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This article, titled "[Retracted] MicroRNA-336 directly targets Sox-2 in osteosarcoma to inhibit tumorigenesis," was published in Molecular Medicine Reports in 2017. However, it has since been retracted by the editor due to concerns raised by a reader.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, specifically in figures 3C and D, as well as the tumor images in figure 4A, were similar to data published in other articles by different authors at different research institutes. The editor contacted the authors for an explanation, but did not receive a reply. The editor apologizes for any inconvenience caused. [Extracted from the article]

This document is a corrigendum for a paper published in the journal Molecular Medicine Reports. The authors acknowledge an error in Figure 2A of the original publication, where there was an unintentional duplication of an image and incorrect sample numbers. The revised version of Figure 2, which shows the correct data, is provided. The authors state that these errors did not significantly impact the results or conclusions of the paper. They emphasize the importance of a larger sample size for future studies and apologize for any inconvenience caused. The document also includes a graph and data on the expression levels of centromere protein M (CENPM) in various types of human cancer. [Extracted from the article]

The myelin and lymphocyte protein (MAL) family is a novel gene family first identified and characterized in 2002. This family is comprised of seven members, including MAL, MAL2, plasmolipin, MALL, myeloid differentiation-associated marker (MYADM), MYADML2 and CMTM8, which are located on different chromosomes. In addition to exhibiting extensive activity during transcytosis, the MAL family plays a vital role in the neurological, digestive, respiratory, genitourinary and other physiological systems. Furthermore, the intimate association between MAL and the pathogenesis, progression and metastasis of malignancies, attributable to several mechanisms such as DNA methylation has also been elucidated. In the present review, an overview of the structural and functional properties of the MAL family and the latest research findings regarding the relationship between several MAL members and various cancers is provided. Furthermore, the potential clinical and scientific significance of MAL is discussed and directions for future research are summarized. [ABSTRACT FROM AUTHOR]

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]

Transcatheter arterial embolization (TAE) therapy has been used in the treatment of inoperable hepatocellular carcinoma (HCC). However, tumor recurrence and metastasis are common in patients after TAE, and these processes may be caused by circulating tumor cells (CTCs). Epithelial-mesenchymal transition (EMT) serves important roles in CTCs, and abnormal expression and activation of epidermal growth factor receptor (EGFR) is common in cancer cells. Afatinib is an EGFR-tyrosine kinase inhibitor (TKI). The present study aimed to investigate the effects of afatinib on EMT and tumorigenesis in HCC cells. Western blot analysis suggested that afatinib was able to effectively suppress overactivation of EGFR. Moreover, the expression levels of EMT- and metastasis-associated genes were found to be modulated by afatinib through EGFR inhibition. In addition, Cell Counting Kit-8 and Transwell assays suggested that the viability, migration and invasion of HCC cells were inhibited by afatinib through EGFR inhibition. Furthermore, the activity of the ERK signaling pathway and the expression levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP9) were decreased following treatment with afatinib in vitro. Collectively, the present results suggested that the inhibitory effects of afatinib on EMT and tumorigenesis may be associated with the ERK-VEGF/MMP9 signaling pathway. The present study provides new insights into understanding the mechanism underlying HCC and may facilitate the development of novel therapeutic strategies to treat HCC recurrence. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level. Aberrant expression of miR-9 has been reported to be involved in the tumorigenesis and progression of various malignancies. However, its role in prostate cancer (PC) has not been completely clarified. In the present study, miR-9 expression was examined in different PC cell lines, patient tissues and a mouse model. Cell Counting Kit-8 and BrdU immunofluorescence assays were performed to assess the effect of miR-9 on the viability of PC cells, while Transwell and wound-healing assays were utilized to evaluate the migration and invasion of PC cells expressing miR-9. Furthermore, a dual-luciferase reporter assay was performed to verify whether mitogen-activated protein kinase kinase kinase 3 (MEKK3) was a direct target of miR-9. The results demonstrated significant downregulation of miR-9 expression in different PC cell lines and 31 human PC tissues, as compared with that in a normal prostate cell line and adjacent normal tissues, respectively. By contrast, upregulation of MEKK3 was confirmed in human PC tissue samples, with its level inversely associated with miR-9 expression. Overexpression of miR-9 in six different PC cell lines (DU145, LNCaP, 22Rv1, PC-3, C4-2B and VCaP) reduced the cell viability and migration. Furthermore, it was demonstrated that the 3′-untranslated region of MEKK3 was a target of miR-9, and that MEKK3 overexpression prevented the inhibitory effects of miR-9 on the viability, migration and invasion of PC cells. miR-9 overexpressing tumor cells also exhibited growth delay in comparison with control tumor cells in vivo. Taken together, the current study findings provided novel insights into the underlying molecular mechanisms of PC oncogenesis, which may support the development of new therapeutic approaches for the treatment of PC. [ABSTRACT FROM AUTHOR]

CBX3, namely chromobox protein homolog 3, a member of the heterochomatin protein 1 (HP1) family, has been shown to be associated with the tumorigenesis of various types of cancer. The aim of the present study was to assess the biological role and the clinicopathological importance of CBX3 in osteosarcoma. The Oncomine database was utilized to determine the CBX3 expression in sarcoma patients. A retrospective cohort study was conducted to evaluate the prognostic value of CBX3 expression. In addition, correlations between the clinicopathological features of the osteosarcoma patients and CBX3 expression were assessed and involved recurrence, distant metastasis, lymph node metastasis, response to chemotherapy, pathological differentiation, clinical stage, anatomic location, tumor size and age. To investigate the function of CBX3 in osteosarcoma, a small interfering RNA for CBX3 was designed and this was used for the transfection of osteosarcoma MG63 cells. Then, the effects of CBX3 on proliferation, cell cycle distribution and apoptosis of osteosarcoma cells were investigated via CCK-8 assay and cell cycle assay and cell apoptosis analysis, respectively. Based on our findings, upregulation of CBX3 expression was noted both in osteosarcoma and also other sarcoma types, which included pleomorphic liposarcoma, myxofibrosarcoma, myxoid/round cell liposarcoma and dedifferentiated liposarcoma. In addition, based on the retrospective cohort study, CBX3 expression was associated with the disease-free survival (DFS) and overall survival (OS) of the osteosarcoma patients and a large tumor size, high distant metastasis rate and high clinical stage rate. In addition, the proliferation ability was blocked by the knockdown of CBX3 through the application of CBX3 siRNA, and CBX3 knockdown also led to increased apoptosis and cell cycle arrest at G0 and G1 phases in osteosarcoma cells. CBX3 is highly expressed in human osteosarcoma tissues. Meanwhile, high CBX3 is a predictor of the poor prognosis of osteosarcoma patients. To conclude, the growth of osteosarcoma can be promoted by CBX3, which may be used as an independent potential prognostic biomarker for patients suffering from osteosarcoma. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) serve important roles in tumorigenesis and may be used as novel molecular biomarkers for clinical diagnosis. However, the role and molecular mechanisms of circRNAs in cervical cancer (CC) remain unknown. In the present study, circRNA isoform of eukaryotic translation initiation factor 4γ2 (circEIF4G2) was revealed to be significantly upregulated in CC tissues and cell lines. Furthermore, increased expression of circEIF4G2 was associated with poor prognosis in patients with CC. circEIF4G2 knockdown suppressed the malignant features of CC cells, including cell proliferation, colony formation, migration and invasion. Additionally, circEIF4G2 was identified to serve as a sponge for microRNA-218 (miR-218), which targeted homeobox A1 (HOXA1). Furthermore, circEIF4G2 may increase the expression levels of HOXA1 by sponging miR-218. Rescue experiments suggested that transfection with a miR-218 inhibitor attenuated the inhibitory effects of circEIF4G2 knockdown on cell proliferation, migration and invasion. Furthermore, silencing HOXA1 reversed the effects of the miR-218 inhibitor on CC cells. Collectively, the present findings suggested that circEIF4G2 promoted cell proliferation and migration via the miR-218/HOXA1 pathway. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNA/miRs) have been demonstrated to be critical post-transcriptional modulators of gene expression during tumorigenesis. Numerous miRNAs have been revealed to be downregulated in human epithelial ovarian cancer (EOC). In the present study, it was observed that the expression of miR-145 was decreased in EOC tissues and cell lines. Overexpression of miR-145 inhibited the proliferation, migration and invasion of EOC cells. The D-type cyclin 2, cyclin D2 (CCND2), and E2F transcription factor 3 (E2F3) were confirmed to be targets of miR-145. In addition, restoration of these 2 genes significantly reversed the tumor suppressive effects of miR-145. Collectively, the results indicated that miR-145 serves a critical role in suppressing the biological behavior of EOC cells by targeting CCND2 and E2F3. Therefore, miR-145 was suggested to be a potential miRNA-based therapeutic target in ovarian cancer. [ABSTRACT FROM AUTHOR]

Ribonuclease inhibitor (RI), also termed angiogenin inhibitor, acts as the inhibitor of ribonucleolytic activity of RNase A and angiogenin. The expression of RI has been investigated in melanoma and bladder cancer cells. However, the precise role of RI in tumorigenesis, in addition to RI-induced autophagy, remains poorly understood. In the present study, it was demonstrated that RI positively regulated autophagy in human colorectal cancer (CRC) cells as indicated by an increase in light chain 3 (LC3)-II levels. Furthermore, RI regulated cell survival in HT29 cells. In addition, autophagy-associated proteins, including beclin-1 and autophagy-related protein 13, were increased in response to RI-induced autophagy, and the protein kinase B (Akt)/mechanistic target of rapamycin (mTOR)/Unc-51 like autophagy activating kinase (ULK1) pathway may be involved in the activation of autophagy induced by RI overexpression. Taken together, the evidence of the present study indicated that the overexpression of RI induced ATG-dependent autophagy in CRC cells via the Akt/mTOR/ULK1 pathway, suggesting that the upregulation of RI activity may constitute a novel approach for the treatment of human colorectal carcinoma. [ABSTRACT FROM AUTHOR]

Leucine zipper/EF-hand-containing transmembrane protein 1 (LETM1) has been identified as the gene responsible for Wolf-Hirschhorn syndrome (WHS), which is characterized by intellectual disability, epilepsy, growth delay and craniofacial dysgenesis. LETM1 is a mitochondrial inner membrane protein that encodes a homolog of the yeast protein Mdm38, which is involved in mitochondrial morphology. In the present review, the importance of LETM1 in WHS and its role within the mitochondrion was explored. LETM1 governs the mitochondrion ion channel and is involved in mitochondrial respiration. Recent studies have reported that LETM1 acts as a mitochondrial Ca2+/H+ antiporter. LETM1 has also been identified as a K+/H+ exchanger, and serves a role in Mg2+ homeostasis. The function of LETM1 in mitochondria regulation is regulated by its binding partners, carboxyl-terminal modulator protein and mitochondrial ribosomal protein L36. Therefore, we describe the remarkable role of LETM1 in mitochondrial network physiology and its function in mitochondrion-mediated cell death. In the context of these findings, we suggest that the participation of LETM1 in tumorigenesis through the alteration of cancer metabolism should be investigated. This review provides a comprehensive description of LETM1 function, which is required for mitochondrial homeostasis and cellular viability. [ABSTRACT FROM AUTHOR]

NOP2/Sun domain family member 2 (NSUN2) is upregulated in numerous types of tumors and may be implicated in multiple biological processes, including cell proliferation, migration and human tumorigenesis. However, little is known about how NSUN2 serves a role in these processes. In the present study, expression profiles of long noncoding RNAs (lncRNAs) and mRNAs were developed in NSUN2-deficient HepG2 cells by RNA-sequencing analysis. A total of 757 lncRNAs were differentially expressed, 392 of which were upregulated, and 365 were downregulated compared with wild-type HepG2 cells. Moreover, 212 lncRNAs were co-expressed with 368 target mRNAs. It was also observed that 253 pairs of lncRNAs and mRNAs exhibited negative correlations and that 290 pairs had positive correlations. Bioinformatics analysis indicated that these lncRNAs regulated by NSUN2 were associated with 'signal transduction', 'extracellular exosome' and 'calcium ion binding', and were enriched in 'pathways in cancer', 'PI3K-Akt signaling pathway' and 'ECM-receptor interaction pathway'. These results illustrate the landscape and co-expression network of lncRNAs regulated by NSUN2 and provide invaluable information for studying the molecular function of NSUN2. [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]

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and its prognosis remains poor. Epithelial-to-mesenchymal transition (EMT)-induced markers have emerged as key regulators of tumor development and progression in HCC. The aim of the present study was to investigate the role of zinc finger E-box-binding homeobox 1 (ZEB1) in the tumorigenesis of HCC and to elucidate the mechanism underlying the correlation between ZEB1 and vimentin (VIM). The expression levels of ZEB1 and VIM were assessed by immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction analysis in HCC tissues and cell lines. The biological significance of ZEB1 was examined by downregulating the expression of ZEB1 in Huh-7 cells. A luciferase reporter assay was used to investigate the association between ZEB1 and VIM. The expression levels of ZEB1 and VIM were higher in tumor tissues compared with those in adjacent normal tissues, and they were significantly associated with a poor prognosis in patients with HCC, whereas ZEB1 silencing led to the attenuation of HCC cell proliferation, invasion and migration. Furthermore, it was observed that ZEB1 was able to bind to a certain site in the VIM promoter and regulate the transcriptional activity of VIM. Therefore, the present study demonstrated that ZEB1 is a potential biomarker of the tumorigenesis and progression of HCC, and it may regulate transcription of the VIM gene. [ABSTRACT FROM AUTHOR]

Emerging evidence has revealed significant roles for long noncoding RNA (lncRNA) in various biological processes, including cell proliferation, apoptosis and invasion. The lncRNA distal-less homeobox 6 antisense 1 (DLX6-AS1) has been reported to serve as a vital oncogene during tumorigenesis and progression. However, the expression levels and functional roles of DLX6-AS1 in cervical cancer are not yet well understood. In the present study, DLX6-AS1 expression was identified to be significantly upregulated in cervical cancer tissues and cell lines by reverse transcription-quantitative polymerase chain reactions. Knockdown of DLX6-AS1 inhibited cell proliferation and induced cell apoptosis. Bioinformatics analysis predicted that micro RNA (miR)-199a was a direct target of DLX6-AS1. Overexpression of miR-199a counteracted the role of DLX6-AS1 in facilitating proliferation and inhibiting apoptosis in in vitro rescue assays. The present results suggest that DLX6-AS1 acting as a sponge for miR-199a may serve a critical role in the development and progression of cervical cancer. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) are closely associated with cancer metastasis in preclinical models and patients with cancer. However, to the best of the authors knowledge, it remains unknown which type of CTCs may serve the key role in cancer metastasis. The present study investigated the association between the epithelial-mesenchymal transition (EMT) phenotype of CTCs from the peripheral blood and distant metastasis in patients with non-small cell lung cancer (NSCLC). Expression of EMT markers in CTCs from a cohort of patients was detected using Canpatrol™ CTC assays. A total of 110 patients (85 patients with NSCLC and 25 patients with benign diseases) were recruited. Among the 110 patients, 88 (80.0%) were characterized as CTC positive with EMT markers. Receiver operating characteristic curves revealed that E+/M+ CTCs exhibited the highest area under the curve (AUC) value of 0.876 [95% confidence interval (CI), 0.805–0.948; P<0.001) in distinguishing between patients with NSCLC and benign pulmonary diseases, and M+ CTCs had the highest AUC value of 0.723 (95% CI, 0.612–0.833; P<0.001) in differentiating patients with NSCLC with distant metastasis from those with non-distant metastasis. The results indicate the potential predictive value of distant metastasis of the EMT phenotype of CTCs in the peripheral blood of patients with NSCLC. [ABSTRACT FROM AUTHOR]

Spindle and kinetochore-associated protein 2 (SKA2) is essential for regulating the progression of mitosis. In recent years, SKA2 upregulation has been detected in various human malignancies and the role of SKA2 in tumorigenesis has received increasing attention. However, the expression and functional significance of SKA2 in breast cancer are not completely understood. To study the effects of SKA2 on breast cancer, the expression levels of SKA2 in breast cancer tissues and cell lines were evaluated by western blotting, reverse transcription-quantitative polymerase chain reaction and immunohistochemical staining. The results demonstrated that SKA2 expression was increased in breast cancer tissues and cells, and SKA2 overexpression was associated with clinical stage and lymph node metastasis. Functional investigations revealed that SKA2 knockdown in breast cancer cells significantly reduced migration and invasion, and resulted in the decreased expression levels of matrix metalloproteinase (MMP)2 and MMP9. Furthermore, the typical microtubule arrangement was altered in SKA2 small interfering RNA (siSKA2)-transfected cells. Reduced levels of SKA2 also downregulated the expression of epithelial-mesenchymal transition proteins, including fibronectin, N-cadherin and vimentin, whereas there were no alterations in the protein expression levels of E-cadherin. Conversely, upregulation of SKA2 decreased the expression levels of E-cadherin, and increased N-cadherin, fibronectin and vimentin levels. Notably, it was demonstrated that E-cadherin was translocated from the cytoplasm to the nucleus in siSKA2-transfected cells. These results demonstrated that SKA2 may be associated with breast cancer metastasis, and siSKA2 inhibited the invasion and metastasis of breast cancer via translocation of E-cadherin from the cytoplasm to the nucleus. [ABSTRACT FROM AUTHOR]

Colon cancer is the second most lethal malignancy worldwide. A better understanding of colon cancer at the molecular level may increase overall survival rates. Previous studies have indicated that prolyl 4-hydroxylase, β polypeptide (P4HB) is associated with tumorigenesis in colon cancer; however, its role and molecular mechanisms in colon cancer remain unclear. In the present study, the cellular responses to P4HB in human colon cancer cell lines were investigated by proliferation and apoptosis assays, western blotting, and immunohistochemistry. The results showed that expression of P4HB was higher in colon cancer tissues compared within adjacent normal tissues. P4HB knockdown increased the apoptosis of human HT29 cells. Furthermore, P4HB knockdown reduced the activation of signal transducer and activator of transcription 3 (STAT3) and promoted accumulation of reactive oxygen species (ROS). Inhibiting the accumulation of ROS abrogated the increased cell apoptosis induced by P4HB knockdown. Notably, decreased ROS levels effectively antagonized the effects of P4HB on STAT3 inactivation. In conclusion, these findings suggested that P4HB knockdown may induce HT29 human colon cancer cell apoptosis through the generation of ROS and inactivation of the STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]

Glioma is a type of malignant brain tumor. Forkhead box C1 (FOXC1) is a conserved transcription factor that is involved in tumorigenesis; however, the function of FOXC1 in glioma remains unclear. The present study aimed to investigate the effects of FOXC1 silencing on the epithelial-to-mesenchymal transition (EMT) of glioma cells. FOXC1-specific small interfering RNAs were employed to downregulate the expression levels of FOXC1 in glioma cells. The proliferation, migration and invasion of glioma cells were assessed by MTT assay, wound healing assay and Transwell assay. Western blot analysis was performed to reveal the effects of FOXC1 on EMT-associated proteins and β-catenin signaling. The results revealed that, following FOXC1 silencing, the proliferation, migration and invasion of glioma cells were decreased. The expression levels of EMT-associated proteins were also affected. Further examination demonstrated that β-catenin signaling was involved in the effects of FOXC1 on glioma cells. Previous results suggested that overexpression of β-catenin reversed the effects of FOXC1 silencing on glioma cells. The present study demonstrated that FOXC1 may regulate the EMT of glioma cells, potentially via β-catenin signaling. Therefore, FOXC1 may be a potential therapeutic target for the treatment of glioma. [ABSTRACT FROM AUTHOR]

Natural compounds which can block cell transformation due to potential for chemoprevention have received increased attention. The present study aimed to investigate whether aloe emodin, which is present in aloe latex or the roots of the Rheum palmatum L. are able to block epidermal growth factor (EGF)- and tissue plasminogen activator-induced JB6 C141 cell transformation. The aloe emodin treatment was applied to the JB6 C141 cell neoplastic model. The toxicity of aloe emodin was determined. The present study detected the expression level of AKT serine/threonine kinase 1 (AKT), lysine-tRNA ligase MSK1 (MSK1) and cyclin D1 using western blotting. The cell proliferation and cell cycle distribution were also monitored. And when 95-maximal effective dose ranged between 1 and 15 µM, the cell death was evident. Aloe emodin-treated cells had an impaired anchorage-independent growth capability, leading to a dose-dependent reduction of colony formation. Western blotting revealed that aloe emodin had a significant effect on phosphorylation of pyruvate dehydrogenase kinase 1 and glycogen synthase kinase 3β (GSK3β) and AKT was inhibited. The present study determined that the proliferation of JB6 C141 cells was reduced in a dose-dependent manner and the effect may be associated with its inhibition of the G1/S cell cycle transition. Cyclin D1 transcriptional activity was reduced to 25%, 24 h following aloe emodin treatment. The protein expression of cyclin D1 was inhibited. The findings of the present study indicated that aloe emodin may be able to suppress neoplastic cell transformation by inhibiting the extracellular-signal regulated kinase/MSK1 and AKT/GSK3β signaling pathways. It may be a potential natural compound for chemoprevention. [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]

Aberrant DNA methylation is the most common type of epigenetic alteration and is associated with many types of cancer. Although previous studies have provided a few novel DNA methylation markers in hepatocellular carcinoma (HCC), specific DNA methylation patterns and comparisons of the aberrant alterations in methylation between HCC and normal liver cell lines have not yet been reported. Therefore, in the present study the Illumina Infinium HumanMethylation 450K BeadChip was employed to identify the genome-wide aberrant DNA methylation profiles of Huh7 and L02 cells. Following Bonferroni adjustment, 102,254 differentially methylated CpG sites (covering 26,511 genes) were detected between Huh7 and L02 cells. Of those CpG sites, 62,702 (61.3%) sites were hypermethylated (covering 12,665 genes) and 39,552 (38.7%) sites were hypomethylated (covering 13,846 genes). The results of the present study indicated that 40.3% of the CpG sites were in CpG island regions, 20.7% were in CpG shores and 8.8% were in shelf regions. A total of 57.3% hypermethylated CpG sites and 39.4% of the hypomethylated CpG sites had a |β-Difference| ≥50%. Within the significant differentially methylated CpG sites, 490 genes were located within 598 differentially methylated regions. Gene Ontology enrichment analysis revealed that 2,107 differentially methylated genes were associated with 'biological process', 13,351 differentially methylated genes were associated with 'molecular function', and 18,041 differentially methylated genes were associated with 'cellular component'. Kyoto Encyclopedia of Genes and Genomes pathway-based analysis revealed 43 signaling pathways that were associated with 5,195 differentially methylated genes. These results demonstrated that aberrant DNA methylation may be a key and common event underlying the tumorigenesis of Huh7 cells. The present study also identified many subsets of hypo- or hyper-methylated CpG sites, genes and signaling pathways, which have an importance in the occurrence and development of HCC. [ABSTRACT FROM AUTHOR]

Airway epithelial cells (AECs) are the first point of contact with airborne antigens and are able to instruct resident immune cells to appropriate immune responses. Previous studies have shown that the abnormal expression of metastasis-associated lung adenocarcinoma transcript 1 (Malat1) was associated with tumorigenesis, progression, metastasis, and apoptosis in many cancer types. However, little is known about its functional involvement in the cross-talk of AECs with dendritic cells (DCs). The aim of the present study was to identify Malat1 as a novel epithelial cell-derived immune-modulating factor that contributes to the specific inflammatory-immune airway microenvironment. By using an in vitro co-culture model, where layers of AECs can interact with DCs, and transfecting Malat1 siRNA in AECs, AEC-conditioned DCs were harvested for further analysis of the celluar phenotype, secretion of inflammatory chemokines, and expression of apoptotic markers. The present study clearly demonstrated that Malat1 modulates the maturation process, pro-inflammatory cytokine secretion and apoptosis in AECs-conditioned DCs. [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]

Recently, microRNA (miR)‑590‑5p has been shown to inhibit tumorigenesis in colorectal and breast cancer; however, its function in osteosarcoma (OS) requires further investigation. In the present study miR‑590‑5p expression was poorly expressed in OS samples and cell lines when compared with that observed in normal cells. In addition, overexpression of miR‑590‑5p significantly reduced the proliferation, migration and invasion of SAOS2 and U2OS cells in vitro, as well as inhibiting tumor sizes in vivo. The results revealed that miR‑590‑5p directly targeted Kruppel‑like factor 5 (KLF5) in SAOS2 and U2OS cells. Their expression was inversely correlated with OS tissues. Finally, it was demonstrated that overexpression of KLF5 rescued the inhibitory effects of miR‑590‑5p on cell proliferation, migration and invasion. Overall, the results of the present study suggested that the miR‑590‑5p/KLF5 axis may regulate OS progression and thus, may be a novel therapeutic target for the treatment of patients with OS. [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]

MicroRNA-9 (miR-9) is reported to be underexpressed in papillary thyroid carcinoma (PTC) tissues; however, the molecular mechanisms underlying the implication of miR-9 in PTC have yet to be elucidated. The present study aimed to explore the potential roles of miR-9 in PTC. PTC tissue samples and paired non-cancerous adjacent tissues were collected from 60 patients with PTC. The human TPC-1 thyroid gland papillary carcinoma cell line was used to investigate the molecular mechanisms underlying the roles of miR-9 in PTC. The levels of miR-9 and its downstream target gene BRAF were detected through reverse transcription-quantitative polymerase chain reaction. MTT assay and flow cytometry were performed to evaluate cell viability and apoptosis, respectively. A mouse xenograft tumor model was established to observe the effects of miR-9 on thyroid gland tumorigenesis in vivo. The present study revealed that the expression of miR-9 was significantly reduced in PTC tissues compared with paired normal tissues. In addition, miR-9 upregulation suppressed the expression of BRAF in TPC-1 cells in vitro. Luciferase reporter assay demonstrated that BRAF may be a direct target gene of miR-9 in TPC-1 cells. In addition, following transfection with miR-9 mimics, the viability of TPC-1 cells was suppressed and their apoptosis was enhanced; conversely, transfection with miR-9 inhibitor exerted the opposite effects in vitro. miR-9 overexpression or downregulation also affected in vivo PTC tumorigenesis in athymic mice. The present findings suggested that miR-9 may suppress the viability of PTC cells and inhibit tumor growth through directly targeting the expression of BRAF in PTC. [ABSTRACT FROM AUTHOR]