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Lung adenocarcinoma is one of the most fatal types of cancer worldwide, with non-small cell lung cancer being the most common subtype. Therefore, there is need for improved treatment approaches. Tumor growth results from the proliferation of a very small number of tumor stem cells, giving rise to the theory of cancer stem cells (CSCs). Lung CSCs are associated with lung cancer development, and although chemotherapy drugs can inhibit the proliferation of lung cancer cells, they have difficulty acting on lung CSCs. Even if the tumor appears to have disappeared after chemotherapy, the presence of a small number of residual tumor stem cells can lead to cancer recurrence and metastasis. Hence, targeting and eliminating lung CSCs is of significant therapeutic importance. In this study, we cultured A549 cells in sphere-forming conditions using B27, EGF, and bFGF, isolated peripheral blood mononuclear cells (PBMCs), and induced and characterized dendritic cells (DCs). We also isolated and expanded T lymphocytes. DC vaccines were prepared using A549 stem cell lysate or A549 cell lysate for sensitization and compared with non-sensitized DC vaccines. The content of IFN-γ in the supernatant of cultures with vaccines and T cells was measured by ELISA. The cytotoxic effects of the vaccines on A549 cells and stem cells were assessed using the Cytotox96 assay, and the impact of the vaccines on A549 cell migration and apoptosis was evaluated using Transwell assays and flow cytometry. DC vaccines sensitized with human lung CSC lysates induced significant in vitro cytotoxic effects on A549 lung cancer cells and CSCs by T lymphocytes, while not producing immune cytotoxic effects on human airway epithelial cells. Moreover, the immune-killing effect induced by DC vaccines sensitized with lung CSC lysates was superior to that of DC vaccines sensitized with lung cancer cells. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is a prevalent malignancy characterized by poor prognosis and high mortality. The role of triggering receptor expressed on myeloid cells-2 (TREM2) in RCC progression has been increasingly recognized, yet its underlying mechanisms remain to be fully elucidated. The aim of the present study was to assess the effects of TREM2 on RCC cells and its potential mechanisms. Lentiviral transfection was used to knockdown and overexpress TREM2 in RCC cells, and the expression level of TREM2 was evaluated using reverse transcription-quantitative PCR. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to assess the proliferation of the RCC cells. Cell migration and invasion was evaluated using the wound healing assay and Transwell assay, respectively. Western blotting was used to assess the expression levels of TREM2, P53, p-P53, P21 and p-P21 in TREM2 knockdown or overexpression RCC cells. The results demonstrated that the expression level of TREM2 was significantly higher in cancer tissues compared with adjacent normal tissues. The results of the CCK-8 and EdU assays demonstrated that knockdown of TREM2 significantly inhibited the proliferation of RCC cells, whilst overexpression of TREM2 enhanced the proliferation of RCC cells. The results of the wound healing and Transwell assay revealed that, compared with the control group, the overexpression of TREM2 significantly increased the migration and invasion of RCC cells, whereas knockdown of TREM2 significantly decreased the migration of RCC cells. In addition, western blotting demonstrated that the phosphorylation levels of P53 and P21 proteins were significantly increased after TREM2 knockdown in RCC cells. In conclusion, TREM2 is highly expressed in RCC tissues and promotes the migration of RCC cells by inhibiting the P53 signaling pathway. The present study provides new insights into the regulatory effect of TREM2 on RCC and further reveals the potential of TREM2 as a therapeutic target for RCC. [ABSTRACT FROM AUTHOR]

Proprotein convertase subtilisin/kexin type 9 (PCSK9) serves an important role in maintaining plasma cholesterol levels, and fatty acid metabolism is involved in the progression of various types of cancer. In the present study, the role of PCSK9 in the development of esophageal squamous cell carcinoma (ESCC) was investigated. PCSK9 expression was compared between ESCC and normal esophageal epithelial tissues using reverse transcription-quantitative PCR. In addition, the association between PCSK9 expression and clinical staging and prognosis was assessed by immunohistochemistry. The effects of PCSK9 overexpression or knockdown on cell proliferation was evaluated using Cell Counting Kit-8 and colony formation assays. The invasion and migration of cancer cells was assessed using wound healing and Transwell assays. Western blotting was performed to evaluate changes in the expression levels of epithelial-mesenchymal transition (EMT)-related proteins. ELISA was performed to detect the effects of PCSK9 on chemokine (C-C motif) ligand 25 (CCL25) secretion. The results revealed that PCSK9 was highly expressed in ESCC tissues compared with that in normal esophageal tissues, and the high expression of PCSK9 was associated with a poor prognosis. Furthermore, PCSK9 could promote the proliferation, migration and invasion of ESCC cells in vitro. Mechanistically, PCSK9 could promote EMT by secreting CCL25. In conclusion, patients with ESCC may benefit from a novel therapeutic strategy based on these findings. [ABSTRACT FROM AUTHOR]

The article titled "MicroRNA-525 enhances chondrosarcoma malignancy by targeting F-spondin 1" has been retracted from the journal Oncology Letters. The retraction was prompted by concerns raised by a reader regarding the similarity of certain data in the article to previously published articles by different authors. The authors were asked for an explanation but did not respond. The Editor has decided to retract the paper and apologizes for any inconvenience caused. [Extracted from the article]

This article, titled "SOX2 knockdown inhibits the migration and invasion of basal cell carcinoma cells by targeting the SRPK1-mediated PI3K/AKT signaling pathway," was retracted from the journal Oncology Letters. The retraction was prompted by the discovery that certain data presented in the article had already been published in previous articles by different authors at different research institutes. The authors were asked for an explanation but did not respond. The Editor has apologized for any inconvenience caused. [Extracted from the article]

The article titled "[Retracted] MicroRNA-195 inhibits the behavior of cervical cancer tumors by directly targeting HDGF" was published in Oncology Letters in 2017. However, it has since been retracted due to concerns raised by a reader regarding the similarity of certain data in Figure 5C to data from other articles that were under consideration for publication at the same time. The authors were asked for an explanation but did not respond. The editor has apologized for any inconvenience caused. The authors of the retracted article are Rongrong Song, Lin Cong, Guantai Ni, Min Chen, Honmei Sun, Yunxia Sun, and Meiling Chen. [Extracted from the article]

Transforming growth factor-β (TGF-β) signaling pathway serves a pivotal role in the pathogenesis of colorectal cancer (CRC). However, the specific molecular mechanisms by which the TGF-β signaling pathway regulates CRC are still not fully understood. In the present study, metabolomics and transcriptomics were used to screen for key metabolites and regulatory genes most related to the regulation of the TGF-β signaling pathway in CRC. Additionally, reverse transcription-quantitative PCR, western blotting and Transwell assays were performed to assess the process of epithelial-mesenchymal transition (EMT). Metabolomics analysis indicated that TGF-β1 has an impact on purine metabolism, leading to an increase in the purine metabolite inosine. The increase of inosine is essential for facilitating EMT and cell migration in CRC cells. Furthermore, the integrated analysis of metabolomics and transcriptomics data revealed that TGF-β1 induces the expression of laccase domain-containing 1 (LACC1), an enzyme involved in the regulation of inosine. Knockdown of LACC1 resulted in a reduction of TGF-β1-induced alterations in inosine levels, EMT and cell migration in CRC cells. The results of the present study suggest that the TGF-β signaling pathway is involved in the regulation of purine metabolism in CRC through the modulation of LACC1 expression. Furthermore, LACC1 appears to influence EMT and cell migration by elevating the levels of the purine metabolite inosine. [ABSTRACT FROM AUTHOR]

Procaine (PCA), a local anesthetic commonly used in stomatology, exhibits antitumor activity in some human malignancies. However, the precise mechanism underlying PCA activity remains unknown, and its antitumor effect in human tongue squamous carcinoma cells has not been reported. Flow cytometry and western blotting were used to assess the effects of PCA on mitochondrial membrane potential (ΔΨm), intracellular reactive oxygen species (ROS) production, cell cycle and apoptosis. The results suggested that PCA inhibits CAL27 and SCC-15 cell proliferation, and clone formation in a dose-dependent manner. CAL27 cells were more sensitive to PCA than SCC-15 cells. PCA also significantly inhibited cell migration, induced mitochondrial damage, reduced ΔΨm and increased intracellular ROS production. PCA causes G2/M cycle arrest and induces apoptosis. The possible mechanism for the inhibition of human tongue squamous carcinoma cell proliferation is through the regulation of ERK phosphorylation and PI3K/AKT-mediated signaling pathways. The results further suggested that autophagy occurs during PCA-induced apoptosis in CAL27 cells, and the addition of the autophagy inhibitor hydroxychloroquine sulfate further enhanced the sensitivity of PCA to inhibit cell proliferation, indicating that autophagy plays an important role in protecting cancer cells from apoptosis. PCA shows potential as an anticancer drug and its combination with autophagy inhibitors enhances its sensitivity. [ABSTRACT FROM AUTHOR]

Bladder cancer is the most common type of tumor in the urinary system and has a high incidence and mortality rate. Protozoan parasites have recently gained popularity as a research topic for cancer therapy. The present study aimed to evaluate the effect of T. gondii tachyzoite culture supernatants on bladder cancer cells. Bladder cancer 5637 cells were infected with two different genotypes of T. gondii tachyzoite culture supernatants, RH and ToxoDB#9. The effects of T. gondii tachyzoite culture supernatant on cell proliferation were detected using a Cell Counting Kit-8 assay. The effects on cell migration and invasion were evaluated using wound healing and Transwell assays. The effect on the apoptosis rate of the cells was assessed using a TUNEL assay, while the protein levels of Bax and Bcl-2 were analyzed by western blotting. The results indicated that the culture supernatant of T. gondii tachyzoites altered the morphology of bladder cancer 5637 cells, inhibited cell proliferation, reduced cell migration and invasion and promoted apoptosis. The ToxoDB#9-type experimental group showed higher efficacy than the RH-type experimental group in inhibiting bladder cancer cell proliferation, reducing cell migration and invasion and promoting apoptosis. These results indicated that the culture supernatant of T. gondii tachyzoites could be a promising therapeutic agent for the treatment of bladder cancer., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Du et al.)

Triple-negative breast cancer (TNBC) is an aggressive disease with the capability of metastasizing quickly. However, treatment options for patients with TNBC still remain limited. CDK4/6 inhibitors have been approved by the U.S. Food and Drug Administration and are administered for the treatment of hormone receptor-positive breast cancer subtypes, but not yet for TNBC. Although pre-clinical research is being conducted on their efficacy in treating TNBC, acquired resistance to CDK4/6 inhibitors is now a growing clinical problem. One of the identified resistance mechanisms is through the IL-6/STAT3 signaling pathway. In the present study, the CDK4/6 inhibitor, abemaciclib, was tested in combination with the IL-6 inhibitor, bazedoxifene, on human (SUM159 and MDA-MB-231) and murine (4T1) TNBC cell lines. Both abemaciclib and bazedoxifene monotherapies inhibited cell cycle progression and cell viability, migration and invasion, and induced apoptosis; however, the combination treatment exerted a greater effect than either monotherapy. These findings support the concept of CDK4/6 and IL-6 dual inhibition as a novel targeted therapy against TNBC., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Caroland et al.)

The article titled "[Retracted] Downregulated microRNA-140-5p expression regulates apoptosis, migration and invasion of lung cancer cells by targeting zinc finger protein 800" published in Oncology Letters in 2020 has been retracted due to concerns about the integrity of the data presented. Specifically, certain data in the Transwell cell migration assay figure were found to have been previously published by different authors at different research institutes. The authors did not provide an explanation for these concerns, leading to the retraction of the paper. [Extracted from the article]

Cancer is a significant societal, public health and economic challenge in the 21st century, and is the primary cause of death from disease globally. Ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) serves a crucial role in several biochemical processes, including adenosine triphosphate hydrolysis, purine metabolism and regulation of signaling pathways. Specifically, ENPP1, a type II transmembrane glycoprotein and key member of the ENPP family, may be upregulated in tumor cells and implicated in the pathogenesis of multiple human cancers. The present review provides an overview of the structural, pathological and physiological roles of ENPP1 and discusses the potential mechanisms of ENPP1 in the development of cancers such as breast, colon, gallbladder, liver and lung cancers, and also summarizes the four major signaling pathways in tumors. Furthermore, the present review demonstrates that ENPP1 serves a crucial role in cell migration, proliferation and invasion, and that corresponding inhibitors have been developed and associated with clinical characterization. [ABSTRACT FROM AUTHOR]

The article "Jak3 is involved in CCR7-dependent migration and invasion in metastatic squamous cell carcinoma of the head and neck" published in Oncology Letters in 2017 was corrected due to errors in the assembly of data panels in Figure 3B. The authors acknowledged the mistakes and provided a revised version of the figure with the correct data for migration assay experiments. The errors did not impact the overall conclusions of the paper, and the authors expressed gratitude to the Editor of Oncology Letters for allowing them to publish the corrigendum. [Extracted from the article]

In recent years there has been a decline in the incidence of gastric cancer, however the high mortality rate has remained constant. The present study evaluated the potential effects of the retinoid fenretinide on the viability and migration of two cell lines, AGS and NCI-N87, that represented primary and metastatic intestinal gastric cancer subtypes, respectively. It was determined that a similar2 dose of fenretinide reduced the viability of both the primary and metastatic cell lines. In addition, it was demonstrated that combined treatment with fenretinide and cisplatin may affect the viability of both primary and metastatic gastric cancer cells. Furthermore, a wound healing assay demonstrated an inhibitory effect for fenretinide on cell migration. As part of the characterization of the mechanism of action, the effect of fenretinide on reactive oxygen species production and lipid droplet content was evaluated, with the latter as an indirect means of assessing autophagy. These results support the hypothesis of combining using fenretinide with conventional therapies to improve survival rates in advanced or metastatic gastric cancer. [ABSTRACT FROM AUTHOR]

The article titled "[Retracted] SRC-like adaptor protein negatively regulates Wnt signaling in intrahepatic cholangiocarcinoma" published in Oncology Letters in 2019 has been retracted due to concerns raised by a reader. The data presented in Figure 5A and B were found to have been previously published in other research articles by different authors at different institutes. The authors did not provide an explanation for these concerns, leading to the retraction of the paper. [Extracted from the article]

Intrahepatic cholangiocarcinoma (ICC) is a highly invasive malignant tumor. The prognosis of patients with ICC after radical surgical resection remains poor, due to local infiltration, distant metastasis, a high recurrence rate and lack of effective treatment strategies. E26 transformation-specific sequence variant 4 (ETV4) is a pro-carcinogenic factor that is upregulated in several tumors; however, the role of ETV4 in ICC is relatively unknown. The present study aimed to determine the role of ETV4 in the Hccc9810 ICC cell line and to assess how it contributes to epithelial-mesenchymal transition (EMT) in ICC. Hccc9810 cells were infected with lentiviruses to construct stable ETV4-overexpressing cells, stable ETV4 knockdown cells and corresponding control groups. The Cell Counting Kit-8 and Transwell assays were used to quantify cell proliferation, invasion and migration, and the effects on cell cycle progression and apoptosis were detected by flow cytometry. ETV4 was identified as a driver of cell growth, invasion, migration and cell cycle progression, while restraining apoptosis in Hccc9810 cells. Reverse transcription-quantitative PCR and western blotting revealed that increased ETV4 levels may drive EMT by triggering the TGF-β1/Smad signaling pathway. This cascade, in turn, may foster tumor cell proliferation, migration, invasion and cell cycle advancement, and hinder apoptosis. [ABSTRACT FROM AUTHOR]

Smad-ubiquitination regulator 2 (SMURF2) functions as a homolog of E6AP carboxyl terminus-type E3 ubiquitin ligase to regulate cell cycle progression and tumor growth factor expression. SMURF2 has been revealed to function as a tumor suppressor in a number of cancers; however, its function in papillary thyroid carcinoma (PTC) remains largely unknown. Therefore, the aim of the present study was to investigate the function of SMURF2 in PTC. Reverse transcription-quantitative PCR and western blotting were used to detect cellular expression of SMURF2 in vitro. After increasing or inhibiting the expression of SMURF2, MTT was used to detect the effect on tumor cell proliferation and Transwell assays were used to detect the effect on tumor cell migration and invasion. Finally, ELISA was used to detect the effects on glucose and glutamine metabolism in tumor cells and the findings revealed that SMURF2 was downregulated in PTC tissues. Moreover, SMURF2 inhibited the proliferation, invasion and migration of PTC cells, and promoted their apoptosis. Finally, SMURF2 inhibited cell glycolysis and glutaminolysis and affected metabolism in the PTC cell line, TPC-1. Thus, the findings of the present study suggest that SMURF2 may be a potential target in the treatment of PTC. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in the head and neck, and among the OSCCs, tongue squamous cell carcinoma (TSCC) is one of the most common types. Although therapy strategies have recently advanced, the prognosis of TSCC has not substantially improved. Metastasis is one of the main causes of patient mortality in TSCC; therefore, it is necessary to elucidate the mechanism by which TSCC metastasis is regulated. In the present study, the early growth response 1 (Egr-1) expression in TSCC was analyzed based on GEO datasets and the effect of Egr-1 in TSCC tumor cell migration and invasion was measured using Transwell assay. By overexpressing dual-specificity protein phosphatase 1 (DUSP1) in cells with Egr-1 knockdown using lentivirus infection, the role of DUSP1 in Egr-1-regulated TSCC cell migration and invasion was determined. By using luciferase and ChIP assays, the mechanism behind how DUSP1 is regulated by Egr-1 was detected. In the present study, it was demonstrated that Egr-1 was downregulated in TSCC and the knockdown of Egr-1 increased TSCC cell migration and invasion. The expression of Egr-1 was also correlated with DUSP1. The overexpression of DUSP1 in Egr-1 knockdown cells, reduced the level of cell migration and invasion. Furthermore, it was demonstrated that knockdown of Egr-1 inhibited the promoter activity of DUSP1 and the site through which Egr-1 regulates DUSP1 transcription was identified. In conclusion, the present study demonstrated that Egr-1 regulates TSCC cell migration and invasion through modulating DUSP1, suggesting the potential of Egr-1 and DUSP1 as therapy targets for TSCC. [ABSTRACT FROM AUTHOR]

The incidence rates of melanoma have increased steadily in recent decades and nearly 25% of the patients diagnosed with early-stage melanoma will eventually develop metastasis, for which there is currently no fully effective treatment. The link between phospholipases and tumors has been studied extensively, particularly in breast and colon cancers. With the aim of finding new biomarkers and therapeutic options for melanoma, the expression of different phospholipases was assessed in 17 distinct cell lines in the present study, demonstrating that phospholipase D2 (PLD2) is upregulated in metastatic melanoma as compared to normal skin melanocytes. These results were corroborated by immunofluorescence and lipase activity assays. Upregulation of PLD2 expression and increased lipase activity were observed in metastatic melanoma relative to normal skin melanocytes. So far, the implication of PLD2 activity in melanoma malignancies has remained elusive. To the best of our knowledge, the present study was the first to demonstrate that the overexpression of PLD2 enhances lipase activity, and its effect to increase the proliferation, migration and invasion capacity of melanoma cells was assessed with XTT and Transwell assays. In addition, silencing of PLD2 in melanoma cells reduced the metastatic potential of these cells. The present study provided evidence that PLD2 is involved in melanoma malignancy and in particular, in its metastatic potential, and established a basis for future studies evaluating PLD2 blockade as a therapeutic strategy to manage this condition. [ABSTRACT FROM AUTHOR]

The article titled "[Retracted] MicroRNA-425 is downregulated in nasopharyngeal carcinoma and regulates tumor cell viability and invasion by targeting hepatoma-derived growth factor" was published in Oncology Letters in 2018. However, it has since been retracted due to concerns raised by a reader. The reader pointed out that the data presented in Figures 3B and 6C of the article were similar to data from other articles written by different authors at different research institutes, some of which had already been published or were under consideration for publication. The authors were asked for an explanation but did not respond. The Editor of Oncology Letters has apologized for any inconvenience caused. [Extracted from the article]

Human giant larvae-1 (Hugl-1) is a human homologue of Drosophila tumor suppressor lethal (2)-giant larvae and has been reported to be involved in the development of human malignancies. Previous studies performed by our group demonstrated that Hugl-1 inhibits glioma cell proliferation in an intracranial model of nude mice. However, the exact molecular mechanisms underlying the participation of Hugl-1 in glioma invasion and migration, and in the depolarizing process remain largely unknown. Utilizing the U251-MG cells with stable expression of Hugl-1, the present study used wound healing, Transwell invasion and western blot assays to explore the role and specific mechanism of Hugl-1 in glioma invasion and migration. The results of the present study demonstrated that overexpression of Hugl-1 decreased cell-cell adhesion and increased cell-cell extracellular matrix adhesion. In addition, overexpression of Hugl-1 promoted pseudopodia formation, glioma cell migration and invasion. The molecular mechanism of action involved the negative regulation of N-cadherin protein levels by Hugl-1. Overexpression or knockdown of N-cadherin partially suppressed or enhanced the effects of Hugl-1 on glioma cell migration and invasion, respectively. Furthermore, Hugl-1 inhibited cell proliferation, while promoting cell migration, which suggests that it may serve a two-sided biological role in cellular processes. Taken together, these results suggest that Hugl-1 promotes the migration and invasion of malignant glioma cells by decreasing N-cadherin expression. Thus, Hugl-1 may be applied in the development of targeted and personalized treatment. [ABSTRACT FROM AUTHOR]

Breast cancer is the most commonly diagnosed cancer worldwide. Despite the use of chemotherapeutic drugs, drug resistance has been observed in numerous patients with breast cancer. Epithelial-mesenchymal transition (EMT) is an important initiation step in the process of metastasis, whereby cancer cells move away from the original tumor site. Therefore, the discovery of new substances that suppress EMT is a promising avenue for cancer treatment. The present study investigated the effect of hispidulin, a polyphenolic flavonoid, on EMT in human breast cancer cells in vitro (MCF-7 and HCC38). The EMT-associated mRNA and protein expression levels were measured using reverse transcription-quantitative PCR or western blot analysis. Hispidulin treatment increased the expression levels of EMT-associated epithelial markers and decreased the expression levels of mesenchymal markers in both cells. Transforming growth factor-β1 (TGF-β1) treatment increased breast cancer cell viability (assessed via MTS assay) and EMT induction. However, hispidulin and TGF-β1 co-treatment increased the expression levels of E-cadherin and occludin, while downregulating vimentin expression. Additionally, hispidulin treatment inhibited TGF-β1-induced Smad2/3 signaling and cell migration in both breast cancer cell lines. Overall, the current findings suggested that hispidulin may inhibit EMT and cell migration by suppressing the Smad2/3 signaling pathway in breast cancer cells. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNA molecules that are extensively expressed in a variety of species. Recently, increasing evidence suggests that circRNAs have vital functions indifferent types of human cancer, such as gastric cancer, papillary thyroid cancer and lung cancer. However, the roles of circRNAs in the development of colorectal cancer (CRC) remain unclear. The present study aimed to determine the molecular mechanism underlying hsa_circ_0001696 on the proliferation and migration of CRC cells. Reverse transcription-quantitative PCR analysis was performed to detect hsa_circ_0001696 expression in 18 paired CRC tissues and matched adjacent normal tissues. RNA interference was also performed to decrease hsa_circ_0001696 expression, and its biological effects were further assessed via flow cytometry, wound healing, colony formation and western blot assays. The results demonstrated that hsa_circ_0001696 expression was significantly lower in CRC tissues compared with adjacent normal tissues. Furthermore, hsa_circ_0001696 knockdown promoted cell proliferation and migration, and the number of cell colonies significantly increased. In addition, western blot analysis demonstrated that the protein expression levels of cyclin-dependent kinase 4 (CDK4), cyclin D, cyclin E and matrix metalloproteinase 9 (MMP9) increased. Taken together, the results of the present study demonstrated that hsa_circ_0001696 expression was downregulated in CRC tissues, and inhibition of hsa_circ_0001696 promoted cell proliferation and migration by regulating the levels of CDK4, cyclin D, cyclin E and MMP9. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the second leading cause of cancer-associated mortality worldwide in children and adolescents. ZC3H12D has been shown to negatively regulate Toll-like receptor signaling and serves as a possible tumor suppressor gene. MicroRNAs (miRNAs/miRs) are known to play an important role in the proliferation of human osteosarcoma cells. However, whether miRNAs can affect tumor development by regulating the expression of ZC3H12D has not yet been investigated. The aim of the present study was to investigate the role of miR128-3p in regulating ZC3H12D expression, as well as its function in tumor cell proliferation, apoptosis, and metastasis. Reverse transcription-quantitative PCR, western blotting and dual luciferase reporter assays were performed to analyze the regulation of ZC3H12D expression by miR-128-3p. MTT, colony formation and flow cytometry assays were also used to analyze the effect of miR-128-3p on cell proliferation and apoptosis. A wound healing assay was performed to investigate the cell migration ability. The results demonstrated that miR-128-3p directly targeted ZC3H12D and downregulated its expression, thereby promoting cell proliferation and migration. miR-128-3p overexpression also improved resistance to cisplatin in MG-63 and 143B cell lines, supporting the hypothesis that miR-128-3p may function as an oncogene in osteosarcoma cells. The potential clinical significance of miR-128-3p as a biomarker and therapeutic target provides rationale for further investigation into the miR-128-3p-mediated molecular pathway and how it is associated with osteosarcoma development. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is a common malignant tumor of the female reproductive system. Long non-coding RNAs (lncRNAs) play an important role in OC occurrence and development. Thus, the function and potential mechanism of lncRNA small nucleolar RNA host gene 3 (SNHG3) was explored in the development of OC. The expression of SNHG3, microRNA (miR)-139-5p and Notch homolog 1, translocationassociated (Drosophila) (Notch1) in OC were detected by RT-qPCR or western blot assay. In addition, CCK-8 and wound-healing assays were used to detect OVCAR3 proliferation and migration ability. The targeting relationship of miR-139-5p with SNHG3 or Notch1 was verified through luciferase reporter assay. Rescue experiments were performed to confirm whether SNHG3 could mediate OVCAR3 proliferation and migration through miR-139-5p and Notch1. In OC tissues and cell lines, the expression of SNHG3 and Notch1 were significantly increased, and the expression of miR-139-5p was significantly decreased. SNHG3 inhibition suppressed the proliferation and migration of OVCAR3 cells. Luciferase reporter experiment confirmed that miR-139-5p could target SNHG3 and Notch1. Transfection of miR-139-5p inhibitor significantly reversed the inhibitory effect of SNHG3 knockdown on OVCAR3 proliferation and migration. Moreover, SNHG3 inhibition or miR-139-5p mimic abolished the promotion of Notch1 overexpression on OVCAR3 proliferation and migration. In conclusion, SNHG3 could accelerate the proliferation and migration of OC cells by regulating miR-139-5p and Notch1. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine the impact of microRNA (miRNA/miR)-633 on the biological properties of malignant melanoma cells. Kang-Ai 1 (KAI1), also known as cluster of differentiation 82, is an important transcriptional regulator and tumor suppressor gene present in different types of tumors. miRNAs that potentially bind with KAI1 were predicted via bioinformatics analyses. In total, six putative miRNA regulators of KAI1 were identified in the present analysis, among which miR-633 was upregulated the most in melanoma tissues compared with the control group. The expression levels of miR-633 and KAI1 in melanoma tissues compared with adjacent normal tissues were then assessed. It was found that miR-633 was significantly upregulated in melanoma cells compared with the control group, whereas the expression levels of KAI1 showed the opposite results. miR-633 was predicted to target the 3'-untranslated region of KAI1 using predictive online tools, and results from luciferase reporter assays confirmed the direct regulation of KAI1 promoter activity by miR-633. Furthermore, miR-633 mimics over expression was shown to suppress both mRNA and protein expression of KAI1, while miR-633 inhibition resulted in decreased viability and migrationin melanoma cells in vitro. Taken together, the present study demonstrated, to the best of the authors' knowledge for the first time, that miR-633 exerts an important role in melanoma through targeting KAI1. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumors (GISTs) are the most common pathologic type of mesenchymal tumor in the digestive tract. Patients with GIST face the risk of metastasis, postoperative recurrence and imatinib mesylate (IM) resistance. Mitochondrial Tu translation elongation factor (TUFM) is highly expressed in GISTs, and is associated with oncogenesis, progression and prognosis. There is evidence that TUFM is involved in tumor invasion and metastasis. However, the effect of TUFM on GIST-T1 cells and the IM-resistant GIST-IR cell line remains unclear. The present study aimed to evaluate the effects of TUFM on the proliferation, migration and apoptosis of GIST cells in vitro. TUFM short hairpin (sh)RNA expression plasmids were transfected into GIST-T1 and GIST-IR cells by electroporation. The expression levels of enhanced green fluorescent protein were observed by fluorescence microscopy to evaluate the electroporation efficiency. The expression levels of TUFM were detected by western blot analysis and reverse transcription-quantitative PCR. Cell proliferation was assessed by counting cells and using a Cell Counting Kit-8 assay. Cell migration was analyzed using wound healing and Transwell migration assays. Cell cycle distribution and late apoptosis were assessed by flow cytometry. TUFM shRNA expression plasmids were successfully transfected into the GIST cell line by electroporation. The transfection efficiency was >75%, and the TUFM gene silencing efficiency was 73.2±1.4%. TUFM-knockdown decreased the proliferation and migration capacity of GIST-T1 and GIST-IR cells. The proportion of cells in the pre-G1 stage was increased without change in the proportions of cells in the G1, S and G2/M stages after TUFM silencing in GIST-T1 and GIST-IR cells. TUFM may be related to GIST infiltration and metastatic recurrence, suggesting that TUFM may be an effective target for preventing the progression and metastasis of GISTs. [ABSTRACT FROM AUTHOR]

Aberrantly low expression of NF‑κB inhibitor α (IκBα) is observed in hepatocellular carcinoma (HCC), yet the underlying mechanism via which IκBα regulates HCC remains largely unknown. Therefore, to determine the potential function of IκBα in hepatocarcinogenesis, the present study used immunohistochemistry (IHC) staining to analyze the associations between IκBα protein expression and clinicopathologic characteristics of 107 patients with HCC. It was found that expression of IκBα was significantly associated with tumor recurrence. Moreover, IκBα protein expression was decreased in 107 HCC tissue samples and was positively associated with overall survival. Mechanistically, it was demonstrated that silencing of IκBα activated NF‑κB in both Huh7 and HCCLM3 cells, followed by upregulation of Erbb2 interacting protein (Erbin) at both the mRNA and protein levels, confirmed by reverse transcription‑quantitative PCR and western blotting, to promote cell proliferation and migration. Furthermore, knockdown of Erbin significantly attenuated NF‑κB‑mediated cell proliferation and migration. It was also identified that overexpression of Erbin in HCC tissues promoted both cell proliferation and migration, and was negatively associated with IκBα expression in 107 HCC tissue samples. Thus, these results indicated that downregulation of IκBα promoted HCC tumorigenesis via upregulation of NF‑κB‑mediated Erbin expression. [ABSTRACT FROM AUTHOR]

Receptor for hyaluronic acid (HA)-mediated motility (RHAMM) expression is upregulated in pancreatic ductal adenocarcinoma (PDAC). In the present study, small interfering RNA knockdown was used to investigate the regulatory mechanism and function of RHAMM in PDAC cells. Reverse transcription-quantitative PCR was used to measure the mRNA expression levels of RHAMM, hyaluronan synthases (HAS1, HAS2 and HAS3) and hyaluronidases (HYAL1, HYAL2 and HYAL3) in eight PDAC cell lines. Cell migration was assessed using a Transwell assay, while HA concentration was measured using an ELISA. The results revealed that RHAMM-knockdown significantly increased migration in two PDAC cell lines, significantly decreased migration in one cell line and did not affect migration in the other cell lines, and was positively associated with changes in HA production. There was a linear negative correlation between RHAMM mRNA expression and HA concentration in PDAC cells and tissues. The negative correlation between RHAMM mRNA expression and HA concentration was demonstrated in other models, including SUIT2 cells treated with an HA inhibitor or stimulator and a system involving co-culture of SUIT2 cells and stromal fibroblasts. The present findings demonstrated a negative correlation between RHAMM mRNA expression and HA production in a subset of PDAC cell lines. The efficacy of a therapeutic strategy targeting RHAMM should be carefully evaluated in future studies. [ABSTRACT FROM AUTHOR]

Recently, the nuclear receptor farnesoid X receptor (FXR) has been considered to be a liver tumor suppressor. However, the role of FXR in liver cancer invasion and metastasis remains unclear. The results of the current study demonstrated that FXR suppressed the migratory and invasive capacities of SK‑Hep‑1 cells in vitro and that FXR overexpression inhibited local invasion and lung metastasis of SK‑Hep‑1 xenografts in vivo. Bioinformatics analysis of the gene expression profile of SK‑Hep‑1 cells with different FXR levels indicated that FXR may regulate the Wnt/β‑catenin pathway. Compared with controls, FXR‑overexpressing SK‑Hep‑1 cells exhibited decreased expression of β‑catenin target genes and reduced nuclear translocation of β‑catenin proteins in vitro and in vivo. In conclusion, these results indicated that FXR may suppress SK‑Hep‑1 cell invasion and metastasis by suppressing the Wnt/β‑catenin signaling pathway. The current study provided novel insight into the diagnosis and treatment of liver cancer. [ABSTRACT FROM AUTHOR]

Bioinformatics analyses have shown that transmembrane and coiled-coil domain 1 (TMCO1) may be associated with lung adenocarcinoma. However, to the best of our knowledge, no current research has determined whether TMCO1 is involved in the development of lung adenocarcinoma. The present study aimed to identify the association between TMCO1 and lung adenocarcinoma. The present study demonstrated that the positive immunohistochemical staining of TMCO1 in lung adenocarcinoma tissues was significantly higher compared with paracarcinoma tissues. Additionally, knockdown of TMCO1 was demonstrated to downregulate B-cell lymphoma-2 protein expression levels and upregulate cysteinyl aspartate specific proteinase (caspase)-3 and caspase-9 protein expression levels in A549 cells. These changes resulted in decreased apoptosis of A549 cells uponTMCO1 downregulation. In addition, knockdown of TMCO1 decreased matrix metalloproteinase (MMP)-2 and MMP-9 expression levels. The expression of N-cadherin and vimentin also decreased. By contrast, the expression levels of E-cadherin protein increased. Knockdown of TMCO1 resulted in the inhibition of A549 cell migration. The results of the present study demonstrated that TMCO1 was associated with lung adenocarcinoma and that inhibition of TMCO1 expression levels negatively regulated the apoptosis and migration of lung adenocarcinoma cells. Therefore, the present study suggests the potential for TMCO1 to be used in the clinical treatment of lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease, which frequently presents with distant metastasis. Further understanding of the molecular mechanism of PDAC is helpful to uncover novel and effective therapeutic strategies. DEP domain containing 1B (DEPDC1B) is known to play a role in the carcinogenesis and metastasis of several common types of cancer; however, its biological function and molecular mechanism in PDAC progression remain unclear. In the present study, the expression levels of DEPDC1B were detected in 79 pairs of PDAC and adjacent non‑cancerous tissues. Patients with PDAC that exhibited higher DEPDC1B expression levels, were shown to have a poorer prognosis. Functional studies showed that knocking down DEPDC1B inhibited PDAC cell migration and invasion, while overexpressing DEPDC1B promoted these processes. Western blotting analysis and immunofluorescence demonstrated that DEPDC1B overexpression induced the epithelial‑to‑mesenchymal transition (EMT). Further mechanistic studies revealed that DEPDC1B was able to activate the Akt/glycogen synthase kinase‑3β (GSK3β)/Snail signaling pathway. In conclusion, the results of the present study showed that DEPDC1B may serve as an oncogene that contributes to PDAC cell migration and invasion by inducing EMT via Akt/GSK3β/Snail pathway activation. [ABSTRACT FROM AUTHOR]

Liver cancer is one of the most common and aggressive tumors, and usually leads to a poor clinical outcome. Increasing evidence has demonstrated the important functions of microRNAs (miRs) in tumor progression. miR-574-3p has been reported as a tumor suppressor and potential therapeutic target in various types of cancer. However, the underlying mechanism of the effects of miR-574-3p in liver cancer remains unknown. In the present study, reverse transcription-quantitative PCR was performed to detect miR-574-3p expression in liver cancer tissues, and the influence of miR-574-3p on cell growth was evaluated using the Cell Counting Kit-8 assay, and cell migration and flow cytometry analyses. The present study revealed that miR-574-3p expression was downregulated in liver cancer tissues and cell lines. miR-574-3p overexpression, achieved by transfecting miR-574-3p mimics into liver cancer cells, reduced cell proliferation and migration, and promoted cell apoptosis. Mechanistically, ADAM metallopeptidase domain 28 (ADAM28) was identified as a miR-574-3p target via binding to the 3′-untranslated region of the ADAM28 mRNA. Gain-of-function of miR-574-3p downregulated the expression levels of ADAM28 in liver cancer cells. Additionally, overexpression of ADAM28 significantly attenuated the suppressive effect of miR-574-3p on the growth of liver cancer cells. The present results provide novel insights into the function of the miR-574-3p/ADAM28 signaling pathway in liver cancer. [ABSTRACT FROM AUTHOR]

Interleukin-21 (IL-21) is an important cytokine that is currently being investigated for its potential use in tumor immunotherapy in the future. In tumor cells, IL-21 stimulates the immune response by increasing the cytotoxic activity of natural killer cells, B cells and CD8+ T cells, which in turn induces the apoptosis of tumor cells. The therapeutic effects of IL-21 have been investigated in several types of disease and numerous clinical trials are in progress. The aim of the present study was to determine the role of IL-21 in oral squamous cell carcinoma (OSCC) in vitro. IL-21 expression was detected in OSCC tissues via RT-qPCR, western blotting and immunohistochemistry analyses. The results demonstrated that IL-21 protein expression decreased in OSCC tissues. IL-21 was overexpressed using adenovirus in CAL-27 cells. The Cell Counting Kit-8 assay demonstrated that overexpression of IL-21 inhibited cell proliferation. Furthermore, overexpression of IL-21 inhibited cell migration, detected by the wound healing assay, and promoted cell apoptosis, detected by TUNEL staining and flow cytometry analysis. The results demonstrated that overexpression of IL-21 inhibited activation of the JNK signaling pathway. In conclusion, the findings of the present study suggest that IL-21 may function as a potent antitumor agent in OSCC. [ABSTRACT FROM AUTHOR]

Telomerase has been shown to be associated with a variety of cancer types. To elucidate the role of telomerase in esophageal squamous carcinoma (ESCC), tissue samples from 100 patients with ESCC, and paired paracancerous tissues from 75 of these patients, were collected for use in the present study. Using immunohistochemical analysis, the expression of telomerase reverse transcriptase (hTERT) in the cytoplasm of ESCC cells was revealed to be significantly higher compared with that in paracancerous tissues, and no significant difference was observed between hTERT expression in the nucleus of ESCC and paracancerous tissue cells. Combined analysis revealed that the cytoplasmic hTERT-positive rate of patients with ESCC was significantly associated with pathological grade, N stage and Tumor-Node-Metastasis (TNM) stage; these data support the association between hTERT expression and poor patient prognosis. In vitro experiments demonstrated that hTERT knockdown does not inhibit the proliferation of ESCC Kyse410 or Kyse520 cells, but inhibits their migration and invasion abilities. These findings indicate that hTERT expression is associated with ESCC metastasis. Interestingly, decreased colony-formation ability was observed in Kyse410 cells, but not in Kyse520 cells. Collectively, the results of the present study suggest that hTERT may serve as a potential therapeutic target for ESCC. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the fourth most lethal malignancy and is the second most common cause of cancer-associated mortality worldwide. The development of high-throughput sequencing has enabled the identification of potential biomarkers for the diagnosis and treatment of various types of cancer. Although microRNA-101 (miR-101) has been demonstrated to be a potential biomarker of CRC, its detailed mechanisms remain to be fully discovered. In the present study, overall survival analysis was applied to determine the association between miR-101 and CRC prognosis. Reverse transcription-quantitative PCR (RT-qPCR) was used to examine gene expression levels in tissues and cells. Cell proliferative and apoptotic activities were determined by MTT and flow cytometry assays, respectively. Wound healing and Transwell assays were used to examine CRC cell migration and invasion, respectively. In the present study, RT-qPCR analysis indicated that miR-101 was significantly downregulated in CRC tissues and cells. However, clinical data collected from The Cancer Genome Atlas revealed no significant association between the expression levels of miR-101 and the prognosis of CRC. Additionally, miR-101 inhibited the progression of CRC by directly binding to the 3′-untranslated region of Ras-related protein Rap1b (Rap1b). This was associated with downregulation of Rap1b expression. Furthermore, the overexpression of Rap1b promoted miR-101 mimic-attenuated CRC cell progression. The present study demonstrated that miR-101 may be involved in the repression of the CRC progression by forming a negative feedback loop with Rap1b. The findings revealed the interaction between miR-101 and Rap1b during the progression of CRC, which could aid the development of therapeutic strategies. [ABSTRACT FROM AUTHOR]

Long non-coding RNA (lncRNA) MEG3 is a key biomarker and therapeutic target in lung cancer; however, its underlying molecular mechanism in lung cancer progression remains unclear. The present study demonstrated a novel regulatory axis in lung cancer, lncRNA MEG3/dyskeratosis congenita 1 (DKC1), and further investigated the effects and molecular mechanism of lncRNA MEG3/DKC1 in lung cancer. RT-qPCR and western blot analysis were performed to determine gene and protein expression levels. The RNA immunoprecipitation assay was performed to verify binding between lncRNA MEG3 and DKC1. Flow cytometry analysis was performed to assess cell apoptosis, while the Cell Counting Kit-8 assay was performed to determine cell viability. Transwell and wound healing assays were performed to assess cell invasion and migration, respectively. Telomerase activity was measured using the quantitative TeloTAGGG Telomerase PCR-ELISA kit. The results demonstrated that lncRNA MEG3 was downregulated, while its binding protein, DKC1, was upregulated in lung cancer cells. Furthermore, lncRNA MEG3 inhibited cell proliferation, migration, invasion and telomerase activity in A549 cells by downregulating DKC1. lncRNA MEG3 inhibited non-small cell lung cancer progression by inhibiting telomere function, cell proliferation, telomerase activity, cell migration and invasion via regulation of the DKC1 protein expression. LncRNA MEG3/DKC1 was identified as a novel dual-directional regulatory axis in the present study, acting as a promising target for the treatment of lung cancer. [ABSTRACT FROM AUTHOR]

Hypopharyngeal squamous cell carcinoma (SCC) has a poor prognosis due to local invasion and metastasis. The chemokine receptor CXC chemokine receptor type 4 (CXCR4) and its ligand, stromal cell-derived factor 1 (SDF-1), play roles in tumor progression through unclear mechanisms. For the present study, we used a hypopharyngeal SCC cell line, FaDu, expressing CXCR4. We found that SDF-1 promotes migration and invasion of the FaDu cells. In addition, AMD3100, a specific antagonist of CXCR4, inhibited the binding of SDF-1 to CXCR4, resulting in a significant decrease in the FaDu cell migration induced by SDF-1. Stimulation of CXCR4 with SDF-1 induced an increase in the expression of CD147, a cell membrane protein; and this CD147 upregulation was abrogated by AMD3100. CD147 function-blocking antibodies also abolished the SDF-1-induced FaDu invasiveness. Our results suggested that SDF-1/CXCR4 mediate hypopharyngeal SCC cell migration and that CD147 is involved in the SDF-1/CXCR4-related tumor progression. [ABSTRACT FROM AUTHOR]

The aim of the present study was to analyze the microarray data of human colorectal cancer (CRC) tissues and identify novel therapeutic targets for CRC. Microarray analysis from the GSE73360 and GSE84984 datasets was performed to identify novel long non-coding RNAs (lncRNAs) that were differentially expressed in human CRC tissues. Additionally, small interfering RNAs were used to deplete the expression of the indicated lncRNAs in cells. Colony-formation, wound-closure, and transwell assays were performed on CRC cells to assess their proliferation and migration capacities. Through microarray analysis, SCARNA9L, SLMO2-ATP5E and LOC100132062 were identified as differentially expressed lncRNAs in CRC tissues. The present study demonstrated that the ablation of SCARNA9L inhibited cell proliferation and arrested the cell cycle of SW480 and SW620 CRC cells. Additionally, depletion of SCARNA9L restrained the migration of CRC cells in vitro. Overall, the present study investigated the potential involvement of SCARNA9L in CRC and suggests SCARNA9L as a potential biomarker. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most prevalent primary bone malignancy in children and adolescents. Neoadjuvant chemotherapy combined with surgical resection, the current standard treatment of osteosarcoma, is associated with a 5-year survival rate of only ~70%. Therefore, it is necessary to identify new, more effective treatment strategies for patients with this lethal disease. Enoxacin is a highly effective broad-spectrum fluoroquinolone antibiotic with low toxicity. The drug inhibits the growth and metastasis of numerous tumour types, but its efficacy has not been studied in osteosarcoma. This study assessed the antitumour effects of enoxacin in osteosarcoma 143B cells and in a murine tumour xenograft model. Enoxacin inhibited the proliferation, invasion and migration of 143B cells, as well as inducing their apoptosis. These effects were thought to be mediated by downregulation of Bcl-xL, Bxl-2, matrix metalloproteinase (MMP)2 and MMP9 expression. Enoxacin also significantly impaired the growth of bone tumours in nude mice without affecting their liver or kidney function, or blood cell count. Collectively, these results indicate that enoxacin is a promising new drug for osteosarcoma that warrants further evaluation in clinical studies. [ABSTRACT FROM AUTHOR]

Cervical cancer is a malignant disease and a threat to women's health worldwide. Surgical resection followed by radiotherapy or chemotherapy is the main treatment strategy for cervical cancer; however, patients with cervical cancer, especially those with late-stage disease, may not benefit from these traditional therapies, which results in poor clinical outcome. ALOX12B is a gene encoding lipoxygenase, and a mutation in ALOX12B was detected in lung and breast cancer. Furthermore, ALOX12B is essential to the proliferation of epidermoid carcinoma cells; however, the role of ALOX12B in cervical cancer has not been studied thus far, to the best of our knowledge. In the present study, the expression levels of ALOX12B were reduced in cervical cancer cells by lentiviral transfection, and it was found that both cell proliferation and clone formation ability were significantly reduced, and the cell cycle was blocked at G1 phase. Tumor growth was also suppressed in vivo in a xenograft tumor model, but the migration of tumor cells was not affected by ALOX12B. Subsequently, using western blotting, it was demonstrated that knockdown of ALOX12B decreased the expression levels of PI3K, MEK1, ERK1, C-fos and cdc25. Meanwhile, overexpression of ALOX12B increased the expression levels of these five molecules. Conclusively, ALOX12B promoted cell proliferation in cervical cancer via regulation of the PI3K/ERK1 signaling pathway. The present study may improve our understanding of the molecular mechanisms underlying the function of ALOX12B in cervical cancer and inform new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common malignancies, and the fourth most common cause of cancer-associated mortality globally. The epithelial to mesenchymal transition (EMT) serves an important function in metastatic dissemination and determines the aggressiveness of CRC. However, the regulatory mechanism of EMT in CRC has not yet been elucidated. γ-glutamylcyclotransferase (GGCT) is an important enzyme in glutathione metabolism and highly expressed in numerous forms of cancer, making it a promising therapeutic target. In the present study, GGCT was demonstrated to be highly expressed in CRC tissues, and patients with CRC with a higher expression of GGCT exhibited a worse prognosis compared with patients exhibiting a lower expression of GGCT. This result suggests that GGCT may serve as a novel prognostic marker for CRC. Furthermore, GGCT was indicated to promote CRC cell migration and invasion through regulating EMT-associated genes, including N-cadherin, Vimentin, snail family transcriptional repressor 2 and snail family transcriptional repressor 1. In conclusion, the present study provides novel insights into the mechanism governing CRC migration and invasion, and identified GGCT as a promising therapeutic target that may be used in the treatment of CRC. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is a common malignancy worldwide. The disease has a poor prognosis and a low 5-year survival rate. Therefore, it is necessary to identify new strategies to optimize the treatment of ESCC. Vaccinia-related kinase (VRK1) and barrier-to-autointegration factor 1 (BANF1) are overexpressed in ESCC. In the present study, the roles of VRK1 and BANF1 were explored in the development of ESCC. In the present study, the effects of small interfering (si)RNA-induced downregulation of VRK1 on BANF1 expression were investigated as well as the effects on proliferative and migratory activity of ESCC cells. Western blot analysis indicated that the protein expression levels of BANF1 were decreased following siRNA depletion of VRK1. Furthermore, the depletion of VRK1 expression inhibited the proliferation and migration of ESCC cell lines, and flow cytometry analysis indicated that the depletion of VRK1 triggered cell cycle arrest mainly in the S phase. These results suggested that VRK1 and BANF1 may have pivotal roles in the progression of ESCC. [ABSTRACT FROM AUTHOR]

Increasing evidence supports the essential roles of circular RNAs (circRNAs) and microRNAs (miRNAs/miRs) in different types of human cancer. For example, hsa_circ_0137008 functions as a sponge for mi-338-5p and inhibits the malignant phenotype in colorectal cancer. Furthermore, hsa_circ_RNA_0011780 downregulates FBXW7 by targeting miR-554a and suppressing the progression of non-small cell lung cancer. Thus far, only a single report has identified that the miRNA miR-331-3p exerts a pivotal effect on human colorectal cancer (CRC) evolution. However, both the up- and downstream regulatory mechanisms of miR-331-3p are unclear. In the present study, it was predicted via bioinformatics analysis that the circRNA, hsa_circ_0038646, and the glutamate receptor ionotropic kainate 3 (GRIK3) gene contain binding sites that can interact with miR-331-3p. Thus, hsa_circ_0038646/miR-331-3p/GRIK3 may be a novel therapeutic pathway for CRC. Reverse transcription-quantitative PCR and western blotting analyses were performed, as well as cell proliferation, luciferase reporter and Transwell migration assays. Hsa_circ_0038646 was overexpressed in both CRC cells and tissues, and this aberrant expression was positively related with increasing tumor grade. Knockdown of hsa_circ_0038646 significantly weakened human CRC cell proliferation and migration. It was shown that hsa_circ_0038646 can sponge miR-331-3p to suppress its expression, and that suppression of miR-331-3p can reverse the effects of hsa_circ_0038646 inhibition in CRC cells. It was determined that GRIK3 is a downstream target of miR-331-3p, and that hsa_circ_0038646 could increase the levels of GRIK3 by suppressing miR-331-3p in CRC cells. Restoring GRIK3 expression rescued the weakened CRC cell proliferation and migration following hsa_circ_0038646 knockdown. The present study indicated that hsa_circ_0038646 functions as a tumor promoter in CRC by increasing GRIK3 expression via sponging of miR-331-3p. The hsa_circ_0038646/miR-331-3p/GRIK3 axis may be a novel therapeutic and diagnostic target of CRC. [ABSTRACT FROM AUTHOR]

In China the incidence and mortality rates of colon cancer have been increasing annually. Studies have revealed that CXCR7 is expressed in many tumors. The aim of the present study was to investigate the function of CXCR7 in colon cancer. The expression level of chemokine receptor 7 (CXCR7) in Caco-2 and HCT116 cells was investigated to elucidate the effect of CXCR7 on cell biological behavior. Reverse transcription-quantitative PCR and western blot analysis were used to detect the expression level of CXCR7 in Caco-2 and HCT116 cells after transfection with small interfering (si)RNA. To analyze the in vitro biological function of CXCR7, cell proliferation was measured using a Cell Counting Kit-8 assay, and cell invasion and migration were measured using Matrigel, and Transwell and wound healing assays. siRNAs were successfully transfected into Caco-2 and HCT116 cells and resulted in a decrease in CXCR7 protein and mRNA expression. Downregulation of CXCR7 inhibited Caco-2 and HCT116 cell proliferation, invasion, and migration. Regulation of CXCR7 expression may affect the biological behavior of Caco-2 and HCT116 cells, suggesting that CXCR7 has a potential role in molecular therapy in colon cancer. [ABSTRACT FROM AUTHOR]

In recent years, neutrophil gelatinase-associated lipocalin (NGAL) has been considered to be a key molecule in different cancer types and its carcinogenesis may be related to the NGAL/MMP-9 complex. However, its expression pattern and role in nasopharyngeal carcinoma (NPC) has rarely been reported. In the current study, 158 tumor tissues from NPC patients were collected and immunohistochemistry was performed to determine the NGAL protein expression, to investigate the correlation between its expression and clinical and pathological parameters using Chi square analysis. Furthermore, by over-expressing NGAL in NPC cell lines, biological alteration of NPC cells with respect to cell proliferation, migration and invasion was analyzed. Results suggested that high expression of NGAL predicts better prognosis and longer survival. Overexpression of NGAL significantly reduced the proliferation and migration of NPC cells, and induced the apoptosis by activating caspase 3, 8 and 9, and blocking epithelial-mesenchymal transition by inhibiting mothers against decapentaplegic homolog 2/3 phosphorylation. [ABSTRACT FROM AUTHOR]

Epithelial to mesenchymal transition (EMT) is a feature of several types of human cancer, including oral squamous cell carcinoma (OSCC). In the present study, tumor and margin cell cultures obtained from patients with OSCC were used to determine the expression patterns of certain EMT-associated markers, including vimentin, α-smooth muscle actin, SLUG and SNAIL. In addition, other EMT-associated features, including clonal, proliferative and migratory potential were compared between the two cell types. Cell cultures were generated from tumor and margin tissue samples from 6 patients and cultured up to the fifth passage. EMT marker expression was assessed by reverse transcription-quantitative PCR. Cell proliferation, colony formation and scratch wound healing assays were conducted to characterize the two cell types in terms of proliferation rates, clonality and motility. All of the studied markers were expressed in tumor and margin cells. Although no significant differences were noted with regard to the aforementioned markers, their expression tended to be higher in margin cultures than in tumor cultures. The expressions of the EMT markers were also higher in the fifth passage compared with those noted at the first with a few exceptions. The rates of proliferation and cell migration were decreased during passages, while the number of colonies was increased in both types of cell culture. Tumor and margin cells indicated certain similarities with regard to EMT transition characteristics. [ABSTRACT FROM AUTHOR]

Zinc finger protein 24 (ZNF24) has been demonstrated to regulate proliferation, differentiation and migration as well as invasion in several types of cells. However, the molecular role and clinical effects of ZNF24 in prostate cancer (PCa) remain unclear. The present study revealed that ZNF24 expression is upregulated in PCa, and associated with tumor volume, Gleason score, pathological grade and metastasis. Wound healing and Transwell invasion assays revealed that ectopic ZNF24 expression facilitated cell migration and invasion through the Twist1-induced epithelial-to-mesenchymal transition (EMT) process. In addition, colony formation and Cell Counting Kit-8 assays were used to determine the regulatory effects of ZNF24 on proliferation. The results suggested that ZNF24 also promoted cell proliferation in PCa. ZNF24 acted as an oncogene and promoted migration, invasion and EMT of PCa cells via the regulation of Twist1. [ABSTRACT FROM AUTHOR]

Tropomodulin-1 (TMOD1) is a key regulator of actin dynamics, which caps the pointed end of actin filaments. TMOD1 has been reported to be involved in several cellular processes, including neurite outgrowth, spine formation and cell migration. Increasing evidence demonstrates that TMOD1 is implicated in several aspects of cancer development. The present study aimed to investigate the role of TMOD1 in cervical cancer. HeLa and CaSki cell lines, derived from human cervical cancer, were used to evaluate the function of TMOD1. Cell motility was measured via a wound-healing assay, with the TMOD1 short hairpin (sh)RNAs transfected cells. Subsequently, cell proliferation was assessed using low serum cell culture condition, while cell cycle distribution was analyzed via flow cytometry. The results demonstrated that downregulated TMOD1 promoted cell motility and proliferation, which is attributed to promotion of G1/S phase transition in HeLa and CaSki cells. Furthermore, it was indicated that co-expression of shRNA resistant TMOD1 rescued these phenomena. The clinical data demonstrated that high TMOD1 expression is associated with good pathological status in patients with cervical cancer. Overall, the results of the present study indicated that TMOD1 may act as a tumor suppressor in cervical cancer, whereby its downregulated expression was demonstrated to have direct effects on cell motility and cell proliferation. These results provide new evidence for the prognostic prediction of cervical cancer, which may serve as a promising therapeutic strategy for patients with cervical cancer. [ABSTRACT FROM AUTHOR]

MicroRNA (miR)-21 is known to act as an oncogene in cervical cancer by promoting cell proliferation and migration; however, the underlying molecular mechanisms have remained to be fully elucidated. The present study revealed that the gene expression levels of miR-21 and epithelial-mesenchymal transition (EMT)-associated transcription factor Zinc finger E-box-binding homeobox 1 (ZEB1), in cervical cancer and lymphatic metastatic carcinoma tissues were significantly higher than those in normal tissues (P<0.05). Furthermore, the gene expression levels of miR-21 and ZEB1 were positively associated with muscular infiltration depth, parametrical invasion and lymph node metastasis in patients with cervical cancer. Immunohistochemistry assays indicated that the expression levels of ZEB1 and the mesenchymal cell marker Vimentin in cervical cancer tissues were significantly higher than those in normal cervical tissues (P<0.05). Overexpression of miR-21 in HeLa and SiHa cells caused the upregulation of the mesenchymal cell markers Vimentin and N-cadherin, and downregulation of the epithelial cell marker E-cadherin at the proteins level. In addition, overexpression of miR-21 enhanced the invasiveness of HeLa and SiHa cells. These results demonstrated that miR-21 was upregulated in cervical cancer tissues and promoted cell metastasis through modulating EMT. A better understanding of the role of miR-21 and EMT may lead to the development of more effective therapies for patients with cervical cancer. [ABSTRACT FROM AUTHOR]