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The article titled "[Retracted] Long non-coding RNA SNHG6 promotes tumorigenesis in melanoma cells via the microRNA-101-3p/RAP2B axis" was published in Oncology Letters in 2020. However, it has since been retracted by the editor due to concerns raised by a reader. The reader pointed out that certain data in the article's colony formation assay were similar to data from other research articles published by different authors at different research institutes. The authors were asked for an explanation but did not respond. The editor apologizes for any inconvenience caused. [Extracted from the article]

The article titled "[Retracted] LncRNA GAS6 antisense RNA 1 facilitates the tumorigenesis of clear cell renal cell carcinoma by regulating the AMP‑activated protein kinase/mTOR signaling pathway" has been retracted from the journal Oncology Letters. A concerned reader brought to the editor's attention that certain data in the article were similar to data from other articles written by different authors at different research institutes. Some of this data had already been published prior to the submission of this article. The authors were asked for an explanation but did not respond. The editor apologizes for any inconvenience caused. [Extracted from the article]

MicroRNA (miR)‑23b‑3p plays an important role in tumor growth, proliferation, invasion and migration in pancreatic cancer (PC). However, the function and mechanistic role of miR‑23b‑3p in the development of PC remains largely unknown. In the present study, the miR‑23b‑3p levels in the serum of patients with PC were found to be elevated, and the phosphorylation levels of Janus kinase (JAK)2, PI3K, Akt and NF‑κВ were found to be upregulated. In addition, miR‑23b‑3p was induced in response to interleukin‑6 (IL‑6), which is known to be involved in the progression of PC. Overexpression of miR‑23b‑3p, on the other hand, activated the JAK/PI3K and Akt/NF‑κB signaling pathways in PC cells, as evidenced by miR‑23b‑3p‑induced upregulation of phosphorylated (p‑) JAK2, p‑PI3K, p‑Akt and p‑NF‑κВ, as well as the downregulation of PTEN; and these effects were found to be reversible by miR‑23b‑3p inhibition. Furthermore, miR‑23b‑3p was found to downregulate PTEN by directly targeting the 3'‑untranslated region of PTEN mRNA. Notably, in an in vivo xenograft mouse model, overexpression of miR‑23b‑3p accelerated PC cell‑derived tumor growth, activated the JAK/Akt/NF‑κВ signaling pathway and promoted liver metastasis. In contrast, knockdown of miR‑23b‑3p suppressed tumor growth and metastasis as well as JAK/Akt/NF‑κВ signaling activity. In vivo imaging of the mice further confirmed the metastasis promoting role of miR‑23b‑3p in PC. These results suggested that miR‑23b‑3p enhances PC cell tumorigenesis and metastasis, at least, partially via the JAK/PI3K and Akt/NF‑κB signaling pathways. Therefore, targeting miR‑23b‑3p or the JAK/PI3K and Akt/NF‑κB signalings may be potential therapeutic strategy against PC. [ABSTRACT FROM AUTHOR]

Patients with inflammatory bowel disease (IBD) are at a higher risk of developing colitis-associated colorectal cancer. The aim of the present study was to investigate the role of CD73 in IBD-associated tumorigenesis. A mouse model of colitis-associated tumorigenesis (CAT) induced by azoxymethane and dextran sulfate sodium was successfully constructed. Model mice were injected with CD73 inhibitor or adenosine receptor agonist. Colon length, body weight loss and tumor formation were assessed macroscopically. Inflammatory cytokine measurement and RNA sequencing on colon tissues were performed. Inhibition of CD73 by adenosine 5′-(α,β-methylene) diphosphate (APCP) suppressed the severity of CAT with attenuated weight loss, longer colons, lower tumor number and smaller tumor size compared with the model group. Activation of adenosine receptors using 1-(6-amino-9H-purin-9-yl)-1-deoxy-N-ethyl-β-D-ribofuranuronamide (NECA) exacerbated CAT. Histological assessment indicated that inhibition of CD73 reduced, while activation of adenosine receptors exacerbated, the histological damage of the colon. Increased expression of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-6) in colonic tissue was detected in the NECA group. According to RNA sequencing results, potential oncogenes such as arachidonate 15-lipoxygenase (ALOX15), Bcl-2-like protein 15 (Bcl2l15) and N-acetylaspartate synthetase (Nat8l) were downregulated in the APCP group and upregulated in the NECA group compared with the model group. Therefore, inhibition of CD73 attenuated IBD-associated tumorigenesis, while activation of adenosine receptors exacerbated tumorigenesis in a C57BL/6J mouse model. This effect may be associated with the expression of pro-inflammatory cytokines and the regulation of ALOX15, Bcl2l15 and Nat8l. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is one of the most common malignancies worldwide; however, treatment options other than surgery remain limited. Neoadjuvant chemotherapy has the potential to suppress of gastric tumorigenesis. Garcinol has been reported to exert inhibitory effects on the progression of numerous carcinomas. However, its effects in GC remain unclear. Therefore, the aim of the present study was to investigate the effects of garcinol on the proliferation, invasion and apoptosis of gastric carcinoma cells and then to explore the underlying mechanisms. Garcinol significantly decreased the proliferation and invasion of GC cells and increased apoptosis in a dose-dependent manner. Additionally, the expression of AKTp-Thr308, cyclin D1, Bcl-2, BAX, matrix metalloprotease (MMP-2) and MMP-9 in HGC-27 cells following treatment with garcinol. The results obtained in the present study suggested that garcinol may inhibit gastric tumorigenesis by suppressing the PI3K/AKT signaling pathway. [ABSTRACT FROM AUTHOR]

Pituitary adenoma and meningioma are two of the most common benign tumors in the central nervous system. Pituitary adenoma associated with meningioma (PAM) is a rare disease, the tumorigenesis of which remains unclear. Therefore, the aim of the present study was to investigate the tumorigenesis of PAM. A total of 8,197 patients with pituitary adenoma were analyzed. Furthermore, the clinical data of 57 patients with PAM were compared with patients with multiple endocrine neoplasia 1 (MEN-1) syndrome. Whole exome sequencing (WES) was performed on 23 samples from patients with PAM and the germline mutation was verified by Sanger sequencing. The age of tumor penetrance (age of patients at diagnosis) for PAM was significantly higher than that for patients with MEN-1. Compared with MEN-1 patients, there was a significant association between PAM and female sex (P=0.004). Clonal analysis and phylogenetic tree construction suggested that the pituitary adenoma and meningioma in PAM don't originate from a common progenitor. WES revealed that 5/23 PAM samples had the recurrent germline mutation MEN1 c.1523G>A; p.G508D, which may be a genetic risk factor for PAM. Compared with patients with sporadic pituitary adenoma, the difference was statistically significant (P=0.0004). Compared with wild-type MEN1, there was a significant association between the MEN1 mutation and recurrence of pituitary adenoma, young age and larger diameter of the meningioma. The present study indicated that germline mutations in MEN1 may be associated with the tumorigenesis of PAM. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is highly prevalent and exhibits a high incidence and mortality rate. Hypoxia contributes to tumorigenesis and the progression of pancreatic cancer. To the best of our knowledge, the role of microRNA (miR)-519 has not been investigated in hypoxia-induced pancreatic cancer progression. The purpose of the present study was to elucidate the mechanism underlying miR-519-mediated regulation of pancreatic cancer progression. Reverse transcription-quantitative PCR and western blotting were performed to investigate miR-519 and programmed death ligand 1 (PD-L1) mRNA and protein levels, respectively. Additionally, a Transwell assay was performed to examine the invasiveness of PANC-1 and SW1990 cells. Cells were subsequently stained with Annexin V to determine the apoptotic rate of cells. Furthermore, bioinformatics analysis and a dual-luciferase reporter assay were performed to confirm the direct association between miR-519 and PD-L1, and a xenograft experiment was conducted to test the role of miR-519 in vivo. The results revealed that the expression levels of miR-519 in pancreatic cancer cells were reduced following hypoxia treatment. Furthermore, transfection with miR-519 mimics inhibited PANC-1 and SW1990 cell invasiveness, and induced apoptosis under hypoxic conditions. PD-L1 was also identified as a downstream target of miR-519, and rescued the miR-519 mimic-attenuated tumorigenesis of pancreatic cancer cells under hypoxic conditions. Additionally, treatment with miR-519 mimics significantly suppressed the tumor growth of PANC-1 cells. The results of the present study indicated a novel mechanism of miR-519-mediated tumorigenesis in pancreatic cancer cells under hypoxic conditions. The conclusions may be crucial for the improvement of future pancreatic cancer treatment. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a major contributor to cancer-associated mortality in China and remains a vast challenge worldwide. Although the genetic basis of CRC has been investigated, the uncommonly mutated genes in CRC remain unknown, in particular in the Asian population. In the present study, targeted region sequencing on 22 CRC and 10 paired non-cancerous tissues was performed to determine the genetic pattern of CRC samples in the Chinese population. Driver genes were detected by three distinct softwares, including MutSigCV, oncodriveFM and iCAGES. A total of 1,335 reliable somatic mutations were identified in tumour samples compared with normal samples. Furthermore, mismatch repair (MMR) mutant patients presented significantly higher mutation density compared with MMR wild-type patients. The results from MutSigCV, oncodriveFM and iCAGES analyses simultaneously detected 29 unique driver genes. In addition, the genes APC regulator of WNT signaling pathway, SMAD family member 4, neurofibromin 1, AT-rich interaction domain 5B and nuclear receptor corepressor 1 were the top five most frequently mutated genes in CRC samples, with mutation rates of 68, 36, 36, 32 and 27%, respectively. The findings from the present study may therefore serve as a basis for future investigation on the diagnosis and oncogenesis of CRC. [ABSTRACT FROM AUTHOR]

Depending on the type of cancer, bone morphogenetic protein-9 (BMP-9) can promote or inhibit tumorigenesis; however, the function of BMP-9 in colorectal cancer remains unclear. The aim of the present study was to evaluate the clinicopathological importance of BMP-9 expression in the tumorigenesis of normal colorectal epithelial tissue, and subsequent transformation into adenoma and carcinoma. In addition, the present study aimed to determine the prognostic value of BMP-9 on the survival of patients with colorectal cancer (CRC). A total of 65 patients with pathologically confirmed colorectal adenocarcinoma and a history of adenoma were enrolled. BMP-9 and Ki-67 expression was assessed retrospectively using paraffin-embedded samples of normal colorectal mucosa, colorectal adenoma and CRC obtained from each patient. The prognostic value of BMP-9 expression was analyzed in a group comprising 48 patients with CRC and a mean follow-up duration of 39.1 months. Bioinformatics analyses were performed in order to validate the results of the present study using published CRC datasets. The results from the present study suggested that the expression of BMP-9 gradually increased during the transition from normal mucosa to adenoma and subsequent adenocarcinoma (P<0.05); however, no significant association between the expression levels of BMP-9 and the clinicopathological parameters of patients was reported. Kaplan-Meier analysis revealed that patients with high expression levels of BMP-9 exhibited shorter overall survival rate than those with low levels of expression (54.7 vs. 41.3 months; log-rank test, P<0.05). Furthermore, regardless of tumor location and the presence of blood vessel tumor emboli, the univariate and multivariate analyses indicated that BMP-9 expression may be an independent prognostic factor for the overall survival rate of patients with CRC. The results of the present study suggested that BMP-9 may serve an oncogenic role and possess prognostic value in CRC. [ABSTRACT FROM AUTHOR]

Ubiquitin-specific peptidase 9X (USP9X) is involved in certain human diseases, including malignancies, atherosclerosis and certain diseases of the nervous system. USP9X promotes the deubiquitination and stabilization of diverse substrates, thereby exerting a versatile range of effects on pathological and physiological processes. USP9X serves vital roles in the processes of cell survival, invasion and migration in various types of cancer. The present review aims to highlight the current knowledge of USP9X in terms of its structure and the possible mediatory mechanisms involved in certain types of cancer, providing a thorough introduction to its biological functions in carcinogenesis and further outlining its oncogenic or suppressive properties in a diverse range of cancer types. Finally, several perspectives regarding USP9X-targeted pharmacological therapeutics in cancer development are discussed. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LAC) is a leading cause of cancer-associated mortalities, particularly in developed countries. The aberrant expression of microRNAs (miRNAs) has been proven to regulate numerous diseases in the past two decades. miRNAs have been identified in almost all human cancer types. In the present study, the role of miR-944 in LAC proliferation was examined. It was identified that miR-944 was downregulated in LAC tissues and cells, and miR-944 overexpression inhibited A549 and H1299 cell proliferation, as determined by the Cell Counting Kit-8 and colony formation assay. Signal transducer and activator of transcription 1 (STAT1) was upregulated in LAC tissues and cells. Kaplan-Meier analysis demonstrated that the 5-year overall survival in patients with high STAT1 levels was significantly reduced, compared with patients with negative and low STAT1 expression. STAT1 was the direct target of miR-944. Additionally, a miR-944 mimic inhibited A549 cell growth in vitro. Collectively, these data demonstrate that miR-944 serves a pivotal role in LAC tumor growth by targeting STAT1. The data obtained indicated that miR-944 may be a novel biomarker and could result in potential therapies for LAC. [ABSTRACT FROM AUTHOR]

Early detection of nasopharyngeal carcinoma (NPC) is of vital importance for improving prognosis and survival rates. MicroRNA (miRNA) are a class of short and non-coding RNA molecules that are capable of inhibiting the translation of mRNA of target genes. Previous studies have revealed that miRNA are involved in tumorigenesis and cancer development. The RNase-resistance of circulating miRNA have made them valuable non-invasive biomarkers, and has therefore drawn particular attention to their therapeutic potential. The aim of the present study was to investigate the expression of the previously uncharacterized miR-639 in NPC. In a study population of 139 patients, higher expression of miR-639 was associated with metastasis, more advanced cancer stages, and lower disease-free survival rates. In vitro experiments involving transfection of human NPC C666-1 and NPC/HK1 cell lines with miR-639 mimics and antagomir indicated that overexpressing miR-639 promoted cell proliferation and migration, suppression of miR-639 inhibited proliferation and migration. The present study provides evidence that miR-639 is differentially expressed in NPC tissues of varying cancer stages, and suggests that quantifying circulating miR-639 may be of importance for non-invasive diagnosis and prognostic evaluation, and may have potential therapeutic utility. [ABSTRACT FROM AUTHOR]

Increasing evidence has indicated that microRNAs (miRNAs/miRs) are associated with tumorigenesis and the development of numerous cancer types. Previous studies have suggested miRNA-491-5p is downregulated in osteosarcoma (OS) and functions as a tumor suppressor. However, the biological roles and underlying mechanisms associated with miR-491-5p function in OS require further exploration. In the present study, it was demonstrated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) that miR-491-5p was downregulated in 36 pairs of OS tissues, compared with in adjacent normal bone tissues. Furthermore, CCK-8 and colony formation assays indicated that miR-491-5p mimics suppressed OS cell proliferation. However, an miR-491-5p inhibitor enhanced cell proliferation. In addition, luciferase reporter assays, RT-qPCR and western blot analysis demonstrated that PKM2 was a direct target of miR-491-5p. The miR-491-5p mimic inhibited the mRNA and protein expression of PKM2, while the miR-491-5p inhibitor promoted PKM2 mRNA and protein expression. In addition, PKM2 overexpression reversed the proliferation-inhibiting effects of miR-491-5p in OS cells. Therefore, these results indicated that miR-491-5p serves as a tumor suppressor in OS cells, which may be important in OS treatment. [ABSTRACT FROM AUTHOR]

The etiology and pathogenesis of bladder cancer (BCa) is complex. MicroRNA (miRNA) has been implicated in BCa. Targeting of signal transducer and activator of transcription 3 (STAT3) by miR-124 to regulate tumorigenesis has been demonstrated in other types of cancer. In the present study, miR-124 levels were downregulated in the BCa T24 cell line and STAT3 was increased in BCa cell lines. Transfection of miR-124 mimics into T24 cells significantly inhibited STAT3 expression. A luciferase assay confirmed that miR-124 directly targeted the STAT3 3′untranslated region to inhibit STAT expression. Knockdown of STAT3 expression led to increased apoptosis of T24 cells and reduced tumor growth in vitro. The results demonstrated the molecular mechanisms and biological functions of the miR-124/STAT3 signal pathway at the cellular level and indicate the potential of miR-124 as a therapeutic target for BCa. [ABSTRACT FROM AUTHOR]

A number of studies have revealed the significance of microRNAs (miRs) in tumorigenesis. Cervical cancer (CC) is one of the most malignant cancer types and is associated with a poor overall survival rate. A previous study demonstrated a critical role of miR-214 in the development of multiple cancer types, but its role in CC remains elusive. In the current study, miR-214 was observed to be downregulated in CC tissues compared with the adjacent non-cancerous tissue. Overexpression of miR-214 reduced the proliferation of CC cells, whereas inhibiting its expression resulted in enhanced proliferation. Furthermore, Enhancer of zeste homolog 2 (EZH2) was demonstrated to be a direct target of miR-214 in CC. An MTT assay demonstrated that upregulating miR-214 expression or knocking down the expression of EZH2 impaired the proliferation of a CC cell line. Low expression of miR-214 was positively associated with tumor differentiation (P=0.037) and tumor stage (P=0.012). Notably, low expression of miR-214 predicted poor prognosis of patients with CC. Consequently, the results of the current study demonstrated that miR-214 functions as a tumor suppressor in CC and may be regarded as a potential therapeutic target in CC. [ABSTRACT FROM AUTHOR]

Myristoylated alanine‑rich C kinase substrate (MARCKS) is a protein kinase C substrate functioning in different physiological and pathological mechanisms. Previous studies have suggested that MARCKS is capable of influencing tumorigenesis and progression. However, a limited number of studies are available regarding the role of MARCKS in oral squamous cell carcinoma (OSCC). The present study primarily examined MARCKS expression in the OSCC tissues. Furthermore, increased expression of MARCKS was confirmed in the majority of OSCC tissues. Increased MARCKS expression was correlated with more advanced tumor stages, lymphatic metastasis and a poorer overall patient survival. Further molecular mechanistic examinations revealed that downregulated MARCKS expression inhibited the proliferation and migration of OSCC cells in vitro through interruption of MARCKS expression. In addition, the present study demonstrated that MARCKS aggravated OSCC progression via the phosphoinositide 3‑kinase/protein kinase B pathway. Accordingly, the present study considered MARCKS to be a promoter of OSCC tumorigenesis and progression, with the potential utility as a biomarker of a poor prognosis. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that the overexpression of H19 may contribute towards development of tumorigenesis in various types of cancer. To investigate the role of H19 in the development of non‑small cell lung cancer (NSCLC), 76 NSCLC tissues samples and their adjacent normal tissue samples were collected. Expression level of H19, and its association with clinicopathological features and overall survival was analyzed. It was found that compared with normal adjacent tissues, H19 expression was elevated in NSCLC tissues along with a decreased miR‑203 expression level. It was also found that patients who were in advanced clinical stages had a higher H19 and a lower miR‑203 expression compared to normal tissues. The overall survival time of patients with higher H19 expression was shorter compared with the lower H19 expression group. Upregulation of A549 enhanced cell proliferation and promoted invasion. Overexpression of H19 stimulated the epithelial‑mesenchymal transition (EMT) process in lung cancer cells and demonstrated typical morphological characteristics of EMT. The level of mesenchymal marker protein, such as Vimentin and SNAI1 increased; while CDH1 protein level decreased. Also, H19 negatively regulated miR‑203. Inhibition of H19 attenuated miR‑203 induced EMT process. Upregulation of H19 contributes to poor clinical features in patients with NSCLC, induces occurrence of EMT, promotes proliferation and stimulates cell invasion in NSCLC cell line through regulating miRNA‑203 mediated EMT. [ABSTRACT FROM AUTHOR]

The present study focused on the roles of members of the Hedgehog (Hh) signaling pathway in the maintenance of malignant biological characteristics, such as tumorigenesis, similar to that of pancreatic tumor cells. Cluster of differentiation (CD)44+CD24+/CD44-CD24- cells were isolated from three different pancreatic cancer cell lines by flow cytometry. Among the three pancreatic cancer cell lines, the SW1990 cell line exhibited the highest percentage of CD44+CD24+ cells, which accounted for 39.9% of the total. The expression of members of the Hh signaling pathway in CD44+CD24+/CD44-CD24- cells was detected using reverse transcription‑polymerase chain reaction and western blot analysis. The results demonstrated that members of the Hh signaling pathway were differentially expressed in CD44+CD24+ cells compared with CD44-CD24-, normal pancreatic duct cells and unsorted SW1990 cells. In addition, lentiviral expression vectors expressing Smoothened (Smo) small interfering RNA (siRNA) were constructed. Following transfection with the lentiviral expression vectors, Smo expression was markedly reduced in CD44+CD24+ cells. The present study represents a preliminary investigation into the biological characteristics of CD44+CD24+ pancreatic cancer cells. [ABSTRACT FROM AUTHOR]

Cervical cancer is a common gynecological malignancy. Hiwi exhibits a high level of expression in cervical cancer cells. However, the effects of Hiwi expression in cervical cancer cells remain unresolved. In the present study, the effects of Hiwi downregulation on the growth and epithelial‑mesenchymal transition of cervical cancer cells were investigated. The results of the present study revealed that the suppression of Hiwi was able to inhibit the proliferation of cervical cancer cells and arrest cell cycle at G1 phase. The downregulation of Hiwi was also revealed to inhibit the epithelial‑mesenchymal transition process of cervical cancer cells by regulating the expression of E‑cadherin, N‑cadherin, vimentin, and snail. The present study demonstrated that the suppression of Hiwi was able to inhibit the growth and epithelial‑mesenchymal transition of cervical cancer cells. Therefore, the results suggest that Hiwi may function as an oncogene in cervical cancer cells and may become a potential target for cervical cancer therapy. [ABSTRACT FROM AUTHOR]

The aryl hydrocarbon receptor (AhR) is a liganddependent transcription factor whose activity is modulated by xenobiotics and physiological ligands. Activation of the AhR by environmental xenobiotics may induce a conformational change in AhR and has been implicated in a variety of cellular processes, including inflammation and tumorigenesis. It is unknown whether the activation of AhR serves a role in modulating the progression of osteosarcoma. The osteosarcoma cell line MG-63, was treated with AhR ligand, 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD). TCDD treatment degrades AhR expression through activation of the AhR signaling pathway, however there were no survival differences observed in MG-63 cells. There were concomitant elevations of cyclooxygenase-2 and receptor activator of nuclear factor-κB ligand secretion from MG-63 cells upon TCDD treatment on a protein and mRNA level at 24 and 72 h. In addition, TCDD treatment also increases the production of prostaglandin E2 on MG-63 cells, and induces the expression of chemokine receptor CXCR4. However, CXCL12 production was not altered in MG-63 cells when stimulated with TCDD. The AhR antagonist CH-223191, blocks the effects on TCDD-induced RANKL, COX-2, PGE2 and CXCR4 changes. In conclusion, these findings suggest that AhR signal therapy should be further explored as a therapeutic option for the treatment of osteosarcoma. [ABSTRACT FROM AUTHOR]

Histone acetyltransferase GCN5 is a critical component of the TGF‑β/Smad signaling pathway in breast cancer cells; however, it remains unknown whether it is involved in the development and progression of breast cancer. The present study investigated the role of GCN5 in the induction of the EMT by TGF‑β1 in breast cancer cells and its underlying molecular mechanism of action. GCN5 activity was elevated and GCN5 mRNA expression and protein expression were increased in MDA‑MB231 cells following stimulation with TGF‑β1. Furthermore, TGF‑β1 stimulation decreased expression of the epithelial cell marker E‑cadherin and increased expression of the mesenchymal cell markers, N‑cadherin and vimentin, as well as the expression of other EMT markers, including snail and slug. However, these changes were reversed following GCN5 knockdown leading to the downregulation of GCN5 expression. GCN5 knockdown also inhibited the viability, migration and invasion of MDA‑MB231 cells, decreased the expression of p‑STAT3, p‑AKT, MMP9 and E2F1, and increased the expression of p21 in MDA‑MB231 cells compared with cells stimulated with TGF‑β1 alone. Therefore, GCN5 may work downstream of TGF‑β/Smad signaling pathway to regulate the EMT in breast cancer. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of global cancer‑associated mortality, therefore it is important to reveal the molecular mechanisms of lung cancer progression and to develop novel therapeutic targets. The results of the present study identified that manganese‑12 acetate (Mn12Ac) was able to significantly inhibit the migration and invasion of A549 cells. Western blotting demonstrated that treatment with Mn12Ac was able to upregulate E‑cadherin, and downregulate N‑cadherin and vimentin. It was also identified by a quantitative polymerase chain reaction analysis that Mn12Ac was able to reduce the mRNA expression levels of EMT‑associated transcription factors Snail, Slug, Twist‑related protein 1 and zinc finger E‑box‑binding homeobox 1. It was also demonstrated that Mn12Ac was able to reduce the expression levels of Wnt and β‑catenin proteins, and suppress the phosphorylation of phosphoinositide 3‑kinase (PI3K) and AKT in A549 cells. Notably, it was revealed that Mn12Ac was able to decrease the mRNA and protein expression levels of programmed death ligand‑1. Taken together, the results suggested that Mn12Ac is able to inhibit cell migration, invasion and EMT in lung cancer cells by regulating the Wnt/β‑catenin and PI3K/AKT signaling pathways. [ABSTRACT FROM AUTHOR]

Corticotropin releasing hormone binding protein (CRHBP) mediates the reaction between corticotropin releasing hormone (CRH) and corticotropin releasing hormone receptors (CRHRs). It is expressed in a number of organs, and the expression of CRHBP is associated with tumorigenesis and cancer progression. The aim of the present study was to investigate CRHBP expression levels in hepatocellular carcinoma (HCC) and its association with patient clinicopathological characteristics as well as prognosis. The expression of CRHBP was examined by immunohistochemistry in 169 HCC tissues and 151 adjacent non‑tumorous tissues. The results were validated by western blotting using patient tissues and liver cancer cell lines. The association of CRHBP expression with clinicopathological patient characteristics and survival rate was analyzed statistically. Expression of CRHBP was detected in 142/151 (94.0%) non‑tumorous liver tissues, and 84/169 (49.7%) HCC tissues (P<0.001). The expression of CRHBP was negatively associated with tumor size (P=0.013), Edmondson Grade (P=0.002), hepatitis B virus antigen (P=0.020), and α‑fetoprotein levels (P=0.014). Patients exhibiting low CRHBP expression were associated with shorter survival time compared with those exhibiting high CRHBP expression (P=0.012). The results of western blotting analysis suggest that reduced CRHBP expression is frequently observable in patients with HCC. Low CRHBP expression in HCC tissues may be a predictor of clinical prognosis and a potential therapeutic target for HCC. [ABSTRACT FROM AUTHOR]

Previous studies have revealed that long noncoding RNAs (lncRNAs) function as crucial regulators in various biological processes, including tumorigenesis. Although the expression of lncRNA TP73‑antisense RNA1 (AS1) has been identified in hepatocellular carcinoma and glioma, the biological function of TP73‑AS1 in gastric cancer (GC) remains unclear. Thus, the present study employed a comprehensive analysis on the function of lncRNA TP73‑AS1 in GC. The aim of the present study was to determine the clinical significance and biological function of TP73‑AS1 in human GC tissues and cells. Additionally, the expression of TP73‑AS1 was increased in GC tissues and cell lines and increased expression level of TP73‑AS1 was associated with poor prognosis in patients with GC. Functional assays revealed that silencing of TP73‑AS1 may suppress cell proliferation and enhance the chemotherapeutic response of GC cells to cisplatin through targeting the high mobility group 1/receptor for advanced glycation endproducts signaling pathway. Collectively, the results of the present study demonstrated that TP73‑AS1 may be a novel lncRNA for the clinical prognosis of GC and a potential therapeutic target for the treatment of GC. [ABSTRACT FROM AUTHOR]

Central neurocytoma (CN) is a rare periventricular tumor of the central nervous system in young adults. Typically, patients with CN exhibit a favorable prognosis, but in certain cases the clinical course is more aggressive. Therefore, investigating effective therapeutic approaches is important. Oridonin has attracted attention due to its antitumor activities. However, the role of oridonin in tumorigenesis and progression remains unknown. The present study examined the antitumor function of oridonin in CN cells, and investigated the underlying molecular mechanism. An MTT assay suggested that treatment with oridonin was able to significantly inhibit the proliferation of CN cells. The annexin V‑fluorescein isothiocyanate/propidium iodide assay and western blot analysis demonstrated that oridonin was able to induce apoptosis and alter the expression of apoptosis‑associated proteins by downregulating anti‑apoptotic protein, B‑cell lymphoma‑2 (Bcl‑2), and upregulating pro‑apoptosis proteins, Bcl‑2‑like protein 4, cleaved caspase‑3 and cleaved poly(ADP‑ribose) polymerase 1. Subsequently, the Wnt/β‑catenin signaling pathway was examined. Western blot analysis indicated that oridonin markedly decreased the expression of β‑catenin, cyclin D1 and v‑myc avian myelocytomatosis viral oncogene homolog. Furthermore, β‑catenin was silenced by small interference RNA or overexpressed in CN cells, and the effect on cell proliferation was examined. The results indicated that silencing of β‑catenin enhanced the inhibitory effect of oridonin on cell growth, whereas the overexpression of β‑catenin attenuated this effect. These data indicated that oridonin inhibited proliferation and induced apoptosis to exert its antitumor activity in CN cells by repressing Wnt/β‑catenin signaling. Therefore, the present study suggested that oridonin might be an effective adjuvant agent, and that the Wnt/β‑catenin signaling pathway may be a potent target for the therapy in CN. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most prevalent cancer and the fourth most common cause of cancer-associated mortality in males and females globally. Aberrant expression of microRNA-539 (miR-539) has been reported in multiple types of cancer. However, miR-539 expression, function and underlying mechanisms have not been clearly elucidated in CRC. In the present study, miR-539 expression was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in CRC tissues and cell lines. The effects of miR-539 on CRC cells were further examined in in vitro studies. In addition, the direct targets of miR-539 in CRC were investigated using bioinformatics, luciferase reporter assays, RT-qPCR and western blotting. miR-539 was revealed to be significantly downregulated in CRC cell lines and tissues. Decreased miR-539 expression was associated with lymph node metastasis and tumor-node-metastasis stage in patients with CRC. Functional assays revealed that the rescue of miR-539 expression attenuated CRC cell proliferation and invasion in vitro. Additionally, SRY-box 4 (SOX4) was validated as a direct target gene of miR-539 in CRC. Furthermore, SOX4 was revealed to be upregulated in CRC tissues at the mRNA and protein level. A significant negative correlation between miR-539 and SOX4 mRNA expression levels was observed in CRC tissues. Furthermore, upregulation of SOX4 partially restored the tumor suppressive effects of miR-539 on CRC cell proliferation and invasion. Taken together, this suggests that miR-539 may serve tumor-suppressive functions in CRC during the process of malignant transformation, by directly targeting SOX4. miR-539/SOX4-based targeted therapy may represent a potential novel treatment for patients with CRC. [ABSTRACT FROM AUTHOR]

Although osteosarcoma (OS) is the most common type of primary bone tumor in adolescents and young adults, its mechanism remains unclear. A previous study by the authors demonstrated that miR-214-3p was upregulated in OS patients. Therefore, the present study aimed to investigate the effect and molecular mechanism of miR-214-3p in OS cells. OS cell lines, U2OS and MNNG/HOS Cl#5, were transiently transfected with miR-214-3p mimics, a control mimic, miR-214-3p inhibitors and a control inhibitor. Subsequent assays revealed that elevated miR-214-3p promoted the proliferative, migratory and invasive abilities of OS cells, while the opposite effects were observed in cells that were transfected with miR-214-3p inhibitors. The interaction between miR-214-3p and cell adhesion molecule 1 (CADM1) 3'untranslated region (UTR) was verified by a dual luciferase assay, which indicated that the relative luciferase activity was decreased in 293T cells that were co-transfected with miR-214-3p mimic and psiCHECK2-CADM1-3'UTR compared with cells that were co-transfected with psiCHECK2-CADM1-3'UTR and control mimic. The knockdown of CADM1 using small-interfering RNA enhanced the proliferative, migratory and invasive abilities of OS cells. Furthermore, downregulated CADM1 expression increased the expression of phosphorylated P44/42 mitogen activated kinase (MAPK). In conclusion, miR-214-3p was able to directly target CADM1 and decrease its expression. This resulted in the activation of the P44/42 MAPK signaling pathway, and thereby promoted the proliferation, migration and invasion of OS cells. [ABSTRACT FROM AUTHOR]

F-box proteins are essential components of the Skp-cullin-F-box complex (a type of E3 ubiquitin ligase), and participate in cell cycle and immune responses through the ubiquitin proteasome system. F-box protein 39 (FBXO39) belongs to the F-box family, which has been reported to be associated with cancer oncogenesis and progression. The present study aimed to investigate the role of FBXO39 in osteosarcoma (OS) cell proliferation and apoptosis in vitro. It was demonstrated that U-2OS cells exhibited high expression of FBXO39 compared with HOS and SaOS-2 osteosarcoma cells. Thus, knockdown of FBXO39 was performed using lentivirus-mediated short hairpin RNA (shRNA) transfection to validate the effect of FBXO39 in U-2OS cells. Western blotting and RT-qPCR analysis were used to confirm the efficiency of infection by analyzing the expression level of FBXO39. Using Celigo-based cell counting and MTT assays, it was demonstrated that FBXO39 knockdown significantly reduced the rate of cell proliferation compared with control. Caspase 3/7 activity assays and fluorescence-activated cell sorting confirmed the induction of apoptosis in U-2OS cells following FBXO39 knockdown. In conclusion, it was demonstrated that FBXO39 knockdown may significantly inhibit proliferation and promote apoptosis of U-2OS cells. Thus, FBXO39 may serve an important role in OS progression. [ABSTRACT FROM AUTHOR]

Yes-associated protein (YAP) serves an essential role in tumorigenesis. However, the potential role and the molecular mechanism underlying the effect of YAP on hepatocellular carcinoma (HCC) cells have not been elucidated. In the current study, it was revealed that YAP expression was increased significantly in HCC cancer tissues and its overexpression was associated with tumor differentiation. The silencing of YAP by small interferring RNA led to the inhibition of HCC cell growth, which was associated with the promotion of apoptosis. The silencing of YAP also decreased the invasive potential of HCC cells and the activity of the phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) signaling pathway. Furthermore, silencing of YAP increased the chemosensitivity of HCC cells to cisplatin (CDDP) through inactivation of the PI3K/AKT signaling pathway. In vivo studies using PDTX model suggested a promotive role for YAP in the growth of HCC and knockdown of YAP increased the anti-tumor activity of CDDP. Taken together, these results revealed that YAP is overexpressed in HCC, and promotes proliferation, invasion and drug resistance of HCC cells. Inhibition of YAP, alone or in combination with traditional chemotherapy, may effectively combat HCC. [ABSTRACT FROM AUTHOR]

Colon cancer stem cells (CSCs), which are highly capable of self-renewal and proliferation, are involved in colon tumorigenesis and response to therapy. CD133 is considered the most robust surface marker for colorectal cancer stem cells. Although the TP53 gene is frequently mutated in colon cancer, it remains not fully understood whether and how tumor protein p53 (p53) is associated with CD133 expression in colon cancer cells. In the present study, the expression of the CSC biomarker CD133 was investigated in terms of p53 status in colorectal carcinoma HCT116 cells. p53 wild-type HCT116 (HCT116 p53+/+) and depleted HCT116 (HCT116 p53−/−) cells were used throughout this study. Cells carrying the CSC biomarkers CD133 and CD44 were examined by flow cytometry. A dual-luciferase reporter assay was employed to further confirm the transcriptional regulation of the CD133 promoter by p53. The results demonstrated that there was a significant difference in the % of CD133-positive cells between the HCT116 p53+/+ cell line (84.84±0.05%) and the HCT116 p53−/− cell line (4.13±0.02%). The mRNA expression levels of CD133 in HCT116 p53+/+ cells were also significantly higher compared with HCT116 p53−/− cells. Knockdown of p53 by specific small interfering RNA greatly reduced the expression of CD133 in HCT116 p53+/+ cells. Transcription factor binding site analysis indicated that there are several p53 binding elements in the CD133 promoter region. A dual-luciferase reporter assay further demonstrated the transcriptional activation of CD133 promoter by p53. In conclusion, these results suggest that p53 positively regulates the expression of CSC marker CD133 in the HCT116 human colon colorectal cancer cell line. p53 may be involved in the initiation and maintenance of colorectal cancer stem cells through regulating the expression of CD133. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) have been investigated as a novel class of regulators of cellular processes, including cell growth, apoptosis and carcinogenesis. lncRNA BRAF-activated non-protein coding RNA (BANCR) has recently been revealed to be involved in tumorigenesis of numerous types of cancer, including papillary thyroid carcinoma, melanoma, non-small cell lung cancer and colorectal cancer. However, the expression profiles and biological relevance of lncRNA BANCR in hepatocellular carcinoma (HCC) has not yet been reported. In the present study, the expression level of BANCR in tumor tissues and para-cancerous tissues was determined by reverse transcription-quantitative polymerase chain reaction in patients with hepatitis B virus (HBV)-associated HCC, and its association with clinicopathological characteristics of patients was analyzed. The results demonstrated that the expression level of BANCR was significantly reduced in tumor tissues in comparison with in para-cancerous tissues (P<0.001). Furthermore, the present study demonstrated that BANCR expression level was closely associated with serum α-fetoprotein levels (P<0.01) and HCC tumor number (P<0.05). To the best of our knowledge, these results revealed for the first time that BANCR downregulated in patients with HBV-associated HCC and BANCR expression level may be a potential valuable diagnosis and therapeutic biomarker in HCC. [ABSTRACT FROM AUTHOR]

Previous studies have indicated that phospholipase A2 (PLA2) may be associated with tumorigenesis in human tissues. The present study aimed to investigate the association between plasma PLA2 activity and the breast cancer (BC) status of patients. Increased plasma PLA2 activity was detected in patients with breast cancer when compared with healthy controls. Plasma samples were obtained from patients with BC (n=169), patients with benign disease (BD; n=80) and healthy controls (n=81). PLA2 activity was assessed using a quantitative fluorescent assay with selective inhibitors. It was demonstrated that increased PLA2 and secretory PLA2 (sPLA2) activity was associated with tumor stage, particularly in patients with late-stage disease. Additionally, smoking, alcohol consumption, body mass index (BMI) and age of patients did not have a significant effect on PLA2 activity. Analysis of receiver operating characteristic curves revealed that plasma PLA2 and sPLA2 activities were increased in BC patients compared with healthy controls. It was concluded that plasma PLA2 activity may serve as a biomarker for patients with BC. [ABSTRACT FROM AUTHOR]

The clinicopathological value and exploration of the potential molecular mechanism of microRNA-183-5p (miR-183-5p) have been investigated in various cancers; however, to the best of the author's knowledge, no similar research has been reported for bladder cancer. In the present study, it was revealed that the expression level of miR-183-5p was notably increased in bladder cancer tissues compared with adjacent non-cancerous tissues (P=0.001) and was markedly increased in the tissue samples of papillary, pathological T stage (T0-T2) and pathological stage (I-II) compared with tissue samples of their counterparts (P=0.05), according to data from The Cancer Genome Atlas. Receiver operating characteristic analysis revealed the robust diagnostic value of miR-183-5p for distinguishing bladder cancer from non-cancerous bladder tissues (area under curve=0.948; 95% confidence interval: 0.919-0.977). Amplification and deep deletion of miR-183-5p were indicated by cBioPortal, accounting for 1% (4/412) of bladder cancer cases. Data from YM500v3 demonstrated that compared with other cancers, bladder cancer exhibited high expression levels of miR-183-5p, and miR-183-5p expression in primary solid tumors was much higher compared with solid normal tissues. A meta-analysis indicated that miR-183-5p was more highly expressed in bladder cancer samples compared with normal counterparts. A total of 88 potential target genes of miR-183-5p were identified, 13 of which were discerned as hub genes by protein-protein interaction. The epithelial-to-mesenchymal transition pathway was the most significantly enriched pathway by FunRich (P=0.0001). In summary, miR-183-5p may participate in the tumorigenesis and development of bladder cancer via certain signaling pathways, particularly the epithelial-to-mesenchymal transition pathway. However, the exact molecular mechanism of miR-183-5p in bladder cancer must be validated by in vitro and in vivo experiments. [ABSTRACT FROM AUTHOR]

DNA methylation is associated with tumorigenesis and may act as a potential biomarker for detecting cervical cancer. The aim of the present study was to explore the methylation status of the paired box gene 1 (PAX1) and the LIM homeobox transcription factor 1 a (LMX1A) gene in a spectrum of cervical lesions in an Eastern Chinese population. This single-center study involved 121 patients who were divided into normal cervix (NC; n=28), low-grade squamous intraepithelial lesion (LSIL; n=32), high-grade squamous intraepithelial lesion (HSIL; n=34) and cervical squamous cell carcinoma (CSCC; n=27) groups, according to biopsy results. Following extraction and modification of the DNA, quantitative assessment of the PAX1 and LMX1A genes in exfoliated cells was performed using pyrosequencing analysis. Receiver operating characteristic (ROC) curves were generated to calculate the sensitivity and specificity of each parameter and cut-off values of the percentage of methylation reference (PMR) for differentiation diagnosis. Analysis of variance was used to identify differences among groups. The PMR of the two genes was significantly higher in the HSIL and CSCC groups compared with that in the NC and LSIL groups (P<0.001). ROC curve analysis demonstrated that the sensitivity, specificity and accuracy for detection of CSCC were 0.790, 0.837 and 0.809, respectively, using PAX1; and 0.633, 0.357 and 0.893, respectively, using LMX1A. These results indicated that quantitative PAX1 methylation demonstrates potential for cervical cancer screening, while further investigation is required to determine the potential of LMX1A methylation. [ABSTRACT FROM AUTHOR]

MicroRNA-32 (miR-32) is associated with tumor progression and poor prognosis in certain malignant tumors. However, the function and clinical relevance of miR-32 in human hepatocellular carcinoma (HCC) has not yet been elucidated. The present study aimed to investigate the expression and prognostic value of miR-32 from liver samples in patients with HCC. The expression of miR-32 was analyzed in HCC and healthy tissues using Gene Expression Omnibus datasets. Reverse transcription-quantitative polymerase chain reaction was used to analyze the levels of miR-32 mRNA in 154 HCC liver samples, 33 of which were paired with adjacent non-tumor tissues. The overall survival (OS) rate in patients with HCC was evaluated using Kaplan-Meier survival analysis, and the factors that may affect the prognosis and survival of patients with HCC were analyzed using univariate (log-rank test) and multivariate Cox proportional hazard models. The present results demonstrated that miR-32 expression levels were significantly upregulated in HCC liver biopsies compared with normal tissues (P<0.05). miR-32 expression was significantly associated with the number of foci and tumor diameter (P<0.05). In addition, Kaplan-Meier analysis revealed that patients with low miR-32 expression had longer OS and disease-free survival compared with those with high miR-32 expression (P<0.01). Altogether, to the best our knowledge, the present study is the first study to indicate the association between increased miR-32 expression with HCC progression and poor prognosis in patients. This suggests that miR-32 may have potential prognostic value and may be used as a tumor biomarker for the diagnosis of patients with HCC. [ABSTRACT FROM AUTHOR]

F-box only protein 31 (FBXO31), initially identified in 2005, is a novel subunit of the S-phase kinase associated protein 1-Cullin 1-F-box ubiquitin ligase. As with other F-box proteins, FBXO31 may interact with several proteins to promote their ubquitination and subsequent degradation in an F-box-dependent manner. It has been revealed that FBXO31 serves a crucial role in DNA damage response and tumorigenesis. However, the expression and function of FBXO31 varies in different types of human cancer. To the best of our knowledge, the present review is the first to summarize the role of FBXO31 in different types of human cancer and determine its underlying mechanisms, thereby paving the road for the design of FBXO31-targeted anticancer therapies. [ABSTRACT FROM AUTHOR]

Spermatogenesis‑associated gene 12 (SPATA12) functions as an inhibitor in spermatogenesis and tumorigenesis. Our previous study demonstrated that SPATA12 may be induced in tumor cells by ultraviolet (UV) C‑mediated DNA damage, suggesting its importance in maintaining genomic integrity. In order to understand whether and how SPATA12 responds to oxidative damage, the present study established a cellular model of oxidative stress by detecting the effect of H2O2 on cell viability and intracellular superoxide dismutase activity, and the levels of glutathione and malondialdehyde (MDA). Quantitative polymerase chain reaction results demonstrated that H2O2 upregulated the expression of SPATA12, and a dual luciferase reporter gene assay indicated that transcription factor activator protein‑1 (AP‑1) was involved in the response of SPATA12 to oxidative stress. Through the exogenous expression of SPATA12, it was identified that SPATA12 decreased the level of reactive oxygen species and MDA, and also may reduce the degree of cellular oxidative damage and apoptosis induced by H2O2. In addition, resveratrol was demonstrated to increase the expression of SPATA12 by activating AP‑1, and it may be used as a nontoxic activator of the SPATA12 gene. In conclusion, these results suggest that SPATA12 is upregulated by oxidative stress via AP‑1, and that the exogenous expression of SPATA12 protects against H2O2‑induced oxidative damage and apoptosis. [ABSTRACT FROM AUTHOR]

Due to the high mortality rate and unsatisfactory treatment options available, hepatocellular carcinoma (HCC) remains one of the most common malignancies and a leading cause of cancer‑associated mortality. Novel therapeutic targets for HCC are urgently required. Advanced RNA sequencing technology enables the identification of considerable amounts of noncoding RNAs (ncRNAs), including small noncoding RNAs and long noncoding RNAs, which exhibit no protein‑coding activities. In this respect, ncRNAs and their regulatory processes are important factors in liver tumorigenesis. The present review focuses on the characteristics and biological roles of ncRNAs in HCC. Potential therapeutic applications of ncRNAs in HCC are also evaluated. [ABSTRACT FROM AUTHOR]

As a major common malignant tumor in women, the malignant behavior of breast cancer, which includes tumorigenesis and metastasis, is associated with estrogen, particularly 17β-estradiol (E2). With accumulating evidence demonstrating that cancer stem-like cells (CSCs) serve a function in the malignant behavior of breast cancer, including metastasis, recurrence and chemoresistance, the effects of E2 on the physiological processes of CSCs have been attracting more attention. In the present study, in order to investigate the effects of E2 on CSCs, CSCs from the MCF7 breast cancer cell line were isolated and treated with 1, 10 and 50 nM E2. Detection of cell proliferation following E2 treatment revealed that 10 nM E2 treatment inhibited cell proliferation, whereas 50 nM E2 treatment resulted in the induction of apoptosis on CSCs. In order to further investigate the effects of E2 treatment on migration, colony formation and the self-renewal capacity of CSCs in vitro, cells were treated with 1 and 10 nM E2. As expected, compared with mock group, the self-renewal capacity of the CSCs was slightly increased by 10 nM E2 treatment, while 1 nM exhibited no observable effect. E2 treatment demonstrated different effects on the proliferation, migration, colony formation and self-renewal capacity of CSCs in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

To assess the effect of low‑molecular‑weight polysaccharides from Agaricus blazei Murrill (ABP‑AW1) as an immunoadjuvant therapy for type 1 T‑helper (Th1) responses in tumorigenesis, C57BL/6 mice were inoculated subcutaneously with ovalbumin (E.G7‑OVA). After 3, 10 and 17 days, the mice were immunized with PBS, OVA alone, or OVA and ABP‑AW1, at low (50 μg), intermediate (100 μg) or high (200 μg) doses. Tumor growth was examined and compared among the groups, as were the following parameters: Splenocyte viability/proliferation, peripheral blood CD4+/CD8+ T cell ratio, serum OVA‑specific IgG1 and IgG2b, secretion of interleukin (IL)‑2 and interferon (IFN)‑γ, and IFN‑γ production on a single cell level from cultured splenocytes. Tumor growth in mice treated with OVA and ABP‑AW1 (100 or 200 μg) was significantly slower, compared with in the other groups at the same time-points. OVA with 100 or 200 μg ABP‑AW1 was associated with a higher number of total splenocytes, a higher ratio of peripheral blood CD4+/CD8+ T‑lymphocytes, higher serum levels of OVA‑specific Th1‑type antibody IgG2b and greater secretion of the Th1 cytokines IL‑1 and IFN‑γ from splenocytes. ABP‑AW1 is a promising immunoadjuvant therapy candidate, due to its ability to boost the Th1 immune response when co‑administered with a cancer vaccine intended to inhibit cancer progression. [ABSTRACT FROM AUTHOR]

KRAS mutations serve a function in tumorigenesis of colorectal cancer (CRC) and guide the use of targeted drugs. However, the prognostic value of KRAS mutations and their subtypes remain controversial. The present study aimed to investigate the correlations between KRAS mutations and clinicopathological characteristics, and their prognostic significance in Chinese patients with metastatic CRC (mCRC). A total of 135 patients with mCRC were analyzed for KRAS mutations. Mutations in codon 12 and 13 were identified in 45 (33.3%) patients. Only 3 patients harbored a mutation of V600E. Compared with male patients, KRAS codon 12 mutations were more common in female patients (P<0.05). KRAS codon 13 mutations tended to arise in right‑sided compared with left‑sided colon cancer (P<0.05). Survival analysis was performed in 101 patients receiving primary tumor resection. Compared with KRAS codon 12 wild‑type, codon 12 mutations were markedly correlated with a poorer survival (log‑rank P=0.002). No prognostic significance was revealed in codon 13 mutations. In univariate analysis, mortality risk was significantly increased by subtypes of G12D and G12V [hazard ratio (HR) =2.313, 95% confidence interval (CI) =1.069‑5.004, P=0.03; HR=2.621, 95% CI=1.057‑6.497, P=0.04, respectively]. The results of the present study suggested that codon 12 mutations, in particular G12D and G12V, predicted a negative prognosis in Chinese patients with mCRC. These findings require further confirmation via prospective studies with larger samples. [ABSTRACT FROM AUTHOR]

Papillary thyroid carcinoma (PTC) is the most common type of endocrine malignancy and accounts for ~80% of thyroid carcinomas in adults and 90% in children. Risk stratification is important for identifying patients at higher risk and, for this reason, recent advances in molecular genetics of thyroid cancer can be applied to provide novel biomarkers useful in understanding tumor behavior. B‑Raf proto‑oncogene, serine/threonine kinase (BRAF) and rat sarcoma (RAS) mutations have been widely studied and appear to have an important role in thyroid tumorigenesis. Somatic telomerase reverse transcriptase (TERT) promoter mutations have been recently identified in several types of malignant tumors, including thyroid neoplasia; however, the actual role of TERT mutations in thyroid tumorigenesis is still under debate. In the present study, the mutational status of BRAF, RAS and TERT was analyzed in order to elucidate the roles of these genes in thyroid tumorigenesis. The TERT mutational analysis was also correlated with an immunohistochemical study of TERT protein expression. According to the literature, our data provide evidence of the BRAF and RAS roles in thyroid tumorigenesis, supporting an association between BRAF (V600E) mutations and the more aggressive clinical and pathological features of thyroid tumors. By contrast, TERT mutations were not significantly associated with any clinical parameters; therefore, its role in initial tumorigenesis should be further investigated. [ABSTRACT FROM AUTHOR]

Tribbles homolog 3 (TRB3), a type of pseudokinase that contains a consensus serine/threonine kinase catalytic core structure, is upregulated in hepatocellular carcinoma. However, the effect of TRB3 expression in hepatocellular carcinoma and the molecular mechanisms underlying TRB3-mediated effects on tumorigenesis in hepatocellular carcinoma have not been fully elucidated. The present study focused on the effect of TRB3 expression in MHCC97H hepatocellular carcinoma cells and investigated the underlying molecular mechanisms in MHCC97H cells. In the present study, it was revealed that TRB3 was significantly overexpressed in the MHCC97H hepatocellular carcinoma cell compared with L-02 normal hepatic cells. Under endoplasmic reticulum (ER) stress induced by thapsigargin and tunicamycin, the levels of TRB3, CCAAT/enhancer binding protein homologous protein (CHOP), protein kinase B (AKT) and phosphorylated (p)AKT expression were upregulated. Furthermore, when the expression of TRB3 was silenced by short hairpin (sh)RNA, the survival of MHCC97H hepatocellular carcinoma cells was increased. Notably, following transduction with lentiviral containing TRB3-shRNA, cell survival also increased after treatment with chemotherapy drug cisplatin. The present study demonstrated that knockdown of CHOP by shRNA was able to reduce TRB3 expression, and the knockdown of TRB3 markedly increased the level of pAKT. TRB3 was overexpressed in MHCC97H hepatocellular carcinoma cells, particularly under endoplasmic reticulum stress. Knockdown of TRB3 was able to increase cell survival. Therefore, TRB3 expression may induce apoptosis and reverse resistance to chemotherapy in MHCC97H hepatic carcinoma cells. The present study suggests that TRB3 is a key molecule that mediates the crosstalk between ER stress and AKT signal pathways. Furthermore, the present study may provide further insight into the cancer biology of hepatocellular carcinoma and the development of anticancer drugs targeting the ER stress and AKT signaling pathways. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is the fourth most common type of malignant tumor worldwide, and causes the second highest number of cancer-associated mortalities in 2012. Gastric tumorigenesis is a multistep and multifactorial process. In the present study, tissue microarray and immunohistochemistry analysis were used to detect cytotoxin-associated gene A (CagA), c-Met, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and Beclin-1 expression in 121 GC tumors and 120 normal gastric tissues. The clinical relevance and prognostic implications of CagA, c-Met, PI3K and Beclin-1 expression in GC patients were analyzed. Furthermore, the Cox proportional hazards model was performed to indicate the independent prognostic factors for GC patients, including various clinicopathological parameters and CagA, c-Met, PI3K and Beclin-1 expression. The results indicated that CagA-positive H. pylori infection, c-Met, PI3K and Beclin-1 may have major roles in the oncogenesis, invasion and lymph node metastasis of GC. The disease-free survival rate was negatively associated with the expression of c-Met and CagA in tissues, and was positively associated with Beclin-1 expression. Overall survival was also negatively associated with the expression of c-Met and PI3K, and was positively associated with Beclin-1 expression. This indicated that c-Met and Beclin-1 may be independent and efficient biomarkers for predicting the DFS of patients with GC. Furthermore, in CagA-positive H. pylori infection-associated GC, c-Met expression was significantly upregulated and Beclin-1 expression was significantly downregulated. CagA-positive H. pylori infection therefore associated with the c-Met signaling pathway and the suppression of autophagy in the neoplasia, invasion and metastasis of GC. [ABSTRACT FROM AUTHOR]

MicroRNA-378 (miR-378) is dysregulated in multiple malignancies and is associated with tumor progression. However, the expression and mechanism of miR-378 in pituitary adenoma (PA) remains to be elucidated. In the present study, the role and mechanism of miR-378 in PA tumorigenesis and development was investigated. It was revealed that the levels of miR-378 expression were markedly downregulated in PA tissues. CCK-8 and wound healing assays revealed that transfection with miR-378 mimics was able to markedly inhibit the proliferation and migration of GH3 cells. Furthermore, quantitative polymerase chain reaction analysis demonstrated that ring finger protein 31 (RNF31) was upregulated in PA specimens and the levels of RNF31 expression was negatively regulated by miR-378. In addition, knockdown of RNF31 markedly suppressed cell proliferation and migration in GH3 cells. In conclusion, the present study provides a molecular basis for the function of miR-378/RNF31 in the progression of human PA, indicating a potential novel target for the treatment of PA. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is one of the most aggressive types of brain malignancy, with resistance to chemotherapy being a primary treatment obstacle. ATPase copper transporting β (ATP7B) is involved in multidrug resistance; however, its expression in GBM remains to be evaluated. In the present study, GBM specimens from 79 patients who underwent gross total tumor removal followed by concomitant temozolomide (TMZ) chemotherapy and radiotherapy were assessed immunohistochemically. The association between the overall survival times of patients and the expression of ATP7B in neoplastic cells was evaluated. In 12/79 tumors (15.2%) >10% of neoplastic cells were immunohistochemically‑positive for ATP7B, and categorized as high‑ATP7B GBM. In the remaining 67 tumors (84.8%) the rate of ATP7B‑positive cells was <10% and recorded as low‑ATP7B GBM. The median overall survival times of patients with high‑ and low‑ATP7B GBM were 14.6, and 24.7 months, respectively. High expression of ATP7B was identified to be associated with shorter overall survival times (hazard ratio, 0.452; 95% confidence interval, 0.206‑0.994; P=0.048). Of the 79 patients, 12 underwent a second operation due to recurrence. These tissue samples were also subjected to immunohistochemical study. The ATP7B positivity rate of tumor cells obtained during the second surgery was significantly higher compared with that in the first surgery (9.17±2.56 vs. 2.75±0.55%; P=0.008). In addition, two ATP7B‑transfected GBM cell lines were identified to be significantly resistant (3.8‑ and 1.7‑fold, respectively) to TMZ compared with the control cell line. The findings of the present study suggest that ATP7B influences GBM resistance to TMZ. [ABSTRACT FROM AUTHOR]

Beclin 1 has a central role in the regulation of autophagy, differentiation, apoptosis resistance, tumorigenesis and cancer progression. The role of Beclin 1 in the development of esophageal squamous cell carcinoma (ESCC) and its subsequent progression is not fully characterized. In the present study, the role of Beclin 1 and autophagy in ESCC was evaluated. The expression of Beclin 1 mRNA and protein levels in human ESCC tumor and adjacent normal esophageal tissue was measured. Beclin 1 mRNA and protein were significantly lower in tumor tissue than in normal esophageal tissue (P<0.05). Cells of the less differentiated esophageal tumors expressed lower Beclin 1 mRNA and protein (P<0.05). Tumors from patients in early clinical stages (I/II) exhibited significantly higher Beclin 1 mRNA and protein expression levels than patients with tumors in mid‑to‑late stages (III/IV; P<0.05). Tumors from patients with lymph node metastasis exhibited significantly lower Beclin 1 mRNA and protein expression levels compared with tumors from patients without lymph node involvement (P<0.05). Beclin 1 downregulation was demonstrated to significantly upregulate invasion by ESCC EC9706 cells (P<0.01), and downregulate the number of acidic vesicular organelles, a process associated with autophagy. These results suggest that the expression of Beclin 1 is associated with the occurrence and development of ESCC. Measuring the Beclin 1 expression of tumors from patient may improve the understanding of the prognosis of patients with ESCC. [ABSTRACT FROM AUTHOR]

Myxoid liposarcoma (MLPS) is the second most common histologic subtype of liposarcoma. However, cartilaginous differentiation within MLPS is an extremely rare phenomenon, with only 7 cases of MLPS with cartilaginous differentiation reported to date. The majority of MLPS cases show the t(12;16)(q13;p11) translocation, resulting in the fused in sarcoma‑DNA damage‑inducible transcript 3 (FUS‑DDIT3) fusion gene. This fusion gene as a hallmark of MLPS is very useful for differential diagnosis from other soft tissue sarcomas, and the associated protein, FUS‑DDIT3, performs an important role in the phenotypic selection of targeted multipotent mesenchymal cells during oncogenesis. In this report, a case of MLPS with cartilaginous differentiation that occurred in the thigh of a 44‑year‑old woman is described. Histopathologically, the tumor was composed of a typical myxoid liposarcoma area and a mature hyaline cartilaginous area. Using fluorescence in situ hybridization analysis, rearrangement of the DDIT3 gene was detected in not only the liposarcomatous area but also in the chondrocytes of the cartilaginous area. Based on these findings, the cartilaginous differentiation area appears to be partially associated with oncogenesis through the specific fusion gene FUS‑DDIT3. [ABSTRACT FROM AUTHOR]

The crosstalk of multiple cellular signaling pathways is crucial in animal development and tissue homeostasis, and its dysregulation may result in tumor formation and metastasis. The Hedgehog (Hh) and Wnt signaling pathways are both considered to be essential regulators of cell proliferation, differentiation and oncogenesis. Recent studies have indicated that the Hh and Wnt signaling pathways are closely associated and involved in regulating embryogenesis and cellular differentiation. Hh signaling acts upstream of the Wnt signaling pathway, and negative regulates Wnt activity via secreted frizzled‑related protein 1 (SFRP1), and the Wnt/β‑catenin pathway downregulates Hh activity through glioma‑associated oncogene homolog 3 transcriptional regulation. This evidence suggests that the imbalance of Hh and Wnt regulation serves a crucial role in cancer‑associated processes. The activation of SFRP1, which inhibits Wnt, has been demonstrated to be an important cross‑point between the two signaling pathways. The present study reviews the complex interaction between the Hh and Wnt signaling pathways in embryogenesis and tumorigenicity, and the role of SFRP1 as an important mediator associated with the dysregulation of the Hh and Wnt signaling pathways. [ABSTRACT FROM AUTHOR]

Fragile histidine triad (FHIT) is a tumor suppressor gene, which is involved in several malignancies. Epigenetic alterations in FHIT have been hypothesized to contribute to tumorigenesis. The present study aimed to examine DNA promoter methylation and gene expression levels of FHIT in childhood acute lymphoblastic leukemia (ALL), in a sample of Iranian patients. The promoter methylation status of FHIT was analyzed in 100 patients diagnosed with ALL and 120 healthy control patients. mRNA expression levels were assessed in 30 new cases of ALL compared with 32 healthy controls. Hypermethylation of the FHIT promoter was significantly more frequent in patients with ALL than in healthy controls (OR=3.83, 95% CI=1.51-9.75, P=0.007). Furthermore, FHIT mRNA expression levels were significantly reduced in childhood ALL patients compared with healthy controls (P=0.032). The results of the present study revealed that dysregulation of the FHIT gene may contribute to the pathogenesis of childhood ALL. Future studies investigating a larger sample population with greater ethnic diversity would be beneficial, to confirm the results from the present study. [ABSTRACT FROM AUTHOR]