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Numerous microRNAs (miRNAs) are dysregulated in tongue squamous cell carcinoma (TSCC), and their dysregulation has been demonstrated to have a strong correlation with TSCC progression via regulation of their targets. Therefore, miRNAs have potential use in the diagnosis and treatment of patients with TSCC. In the present study, miRNA-758 (miR-758) expression in TSCC tissues and cell lines was detected through reverse transcription-quantitative polymerase chain reaction, and the effects of miR-758 on TSCC cell proliferation and invasion were investigated by using Cell Counting kit-8 and Transwell invasion assays. A luciferase reporter assay was performed to determine the target interaction between miR-758 and metadherin (MTDH) in TSCC cells. The results revealed that miR-758 was downregulated in TSCC tissues and cell lines. miR-758 overexpression restricted the proliferation and invasion of TSCC cells. Additionally, MTDH was verified as a direct target gene of miR-758 in TSCC cells. Furthermore, MTDH was observed to be upregulated in TSCC tissues, and the upregulation of MTDH was inversely correlated with miR-758 expression. Moreover, restored MTDH expression significantly counteracted the suppressive effects of miR-758 overexpression on TSCC cells. These results suggested that miR-758 may prevent TSCC progression and development by directly targeting MTDH, thereby providing evidence that miR-758 is a novel therapeutic target for the treatment of patients with TSCC. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs/miRs) serve important roles in regulating gene expression by directly binding to the 3′-untranslated regions of target genes. Multiple miRNAs are dysregulated in retinoblastoma (RB) and their dysregulation is closely related to RB malignancy. Therefore, exploring the detailed roles of miRNAs in RB is valuable to facilitate the development of effective therapeutic targets for patients with this disease. miRNA-874-3p (miR-874) has been recently reported to be downregulated in several types of human cancer and serves an essential role in cancer progression. However, the expression pattern and detailed roles of miR-874 in RB, as well as the underlying molecular mechanisms in RB, have not been clearly elucidated. Therefore, this study detected miR-874 expression in RB tissues and cell lines. The biological roles of miR-874 in RB were determined and the underlying mechanisms of its actions in RB cells were also examined. This study revealed that miR-874 expression was aberrantly underexpressed in RB tissues and cell lines. However, returning miR-874 expression restricted the proliferative and invasive abilities of RB cells. In terms of the underlying mechanism, metadherin (MTDH) was validated as a direct target gene of miR-874 in RB cells. MTDH inhibition could imitate the inhibitory roles of miR-874 overexpression in RB cells. Furthermore, forced MTDH expression partially reversed the suppressive effects of miR-874 on RB cells. In conclusion, this study revealed that miR-874 may inhibit RB progression by directly targeting MTDH. Restoration of miR-874 expression may be a novel strategy for preventing the rapid growth and metastasis of RB cells. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are important regulators of a variety of biological processes and their dysregulation is closely related to cancer formation and progression. Therefore, examination of aberrantly expressed miRNAs in oral squamous cell carcinoma (OSCC) may provide important clues for the diagnosis and treatment of patients with OSCC. The aim of the present study was to determine miRNA (miR)-655-3p expression in OSCC tissues and cell lines, and to investigate the biological roles and mechanisms of miR-655-3p associated with OSCC. Data from the present study indicated that miR-655 expression was significantly downregulated in human OSCC tissues and cell lines. Overexpression of miR-655 attenuated cell proliferation and invasion in OSCC in vitro. Metadherin (MTDH) mRNA was predicted as a potential target of miR-655 by bioinformatics analysis, and this was confirmed by luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction and western blot analysis. In OSCC tissues, MTDH was highly expressed and inversely correlated with miR-655 expression levels. MTDH overexpression reversed the inhibitory effects of miR-655 mimics in OSCC cells. Notably, the upregulation of miR-655 expression inhibited the activation of the phosphatase and tensin homolog (PTEN)/RAC-α serine/threonine-protein kinase (AKT) pathway in OSCC cells. Therefore, these results may provide the first evidence that miR-655 targets MTDH to inhibit proliferation and invasion of OSCC by inhibiting PTEN/AKT signaling. Thus, the restoration of miR-655 expression may be a novel therapeutic strategy for patients with OSCC. [ABSTRACT FROM AUTHOR]

Numerous microRNAs (miRNAs) are aberrantly expressed in glioma, and implicated in glioma occurrence and development. Therefore, the development of miRNAs as potential therapeutic targets for the treatment of patients with glioma has been proposed. miR‑379 has been shown to be aberrantly expressed in the progression of malignant tumours. However, the expression, biological functions and mechanism of miR‑379 in glioma are yet to be fully understood. Hence, the present study aimed to detect miR‑379 expression, investigate its functional relevance and explore its associated molecular mechanism in glioma. In this study, miR‑379 expression was significantly downregulated in glioma tissues and cell lines. Enforced miR‑379 expression markedly suppressed the cell proliferation and invasion of glioma. Metadherin (MTDH) was identified as a direct target of miR‑379 in glioma. The miR‑379 expression and MTDH mRNA levels exhibited an inverse association in glioma tissues. The restoration of the MTDH expression partially rescued the inhibitory effects of miR‑379 overexpression on glioma cell proliferation and invasion, and the upregulation of miR‑379 inhibited the activation of phosphatase and tensin homolog (PTEN)/AKT serine/threonine kinase (AKT) signaling pathway. Overall, these findings demonstrated that miR‑379 may play tumour‑suppressing roles in glioma through downregulation of MTDH and regulation of the PTEN/AKT signaling pathway, suggesting that miR‑379 might be a possible target for the treatment of patients with this malignancy. [ABSTRACT FROM AUTHOR]

Melanoma is derived from melanocytes and accounts for ~80% of skin cancer-associated fatalities worldwide. The dysregulation of microRNAs (miRNAs/miRs) is involved in the development and progression of melanoma. Therefore, miRNAs may be novel diagnostic or prognostic biomarkers and promising therapeutic targets in the treatment of patients with melanoma. miR-675 is differentially expressed in several types of human cancer and has important roles in the pathogenesis of several diseases. However, the expression levels and the biological roles of miR-675 in melanoma remain unclear. Therefore, the present study aimed to assess the expression of miR-675 in melanoma, explore the effects of miR-675 on melanoma cells and investigate the underlying molecular mechanisms that may be involved in the actions of miR-675. The present study indicated that miR-675 expression was downregulated in melanoma tissues and cell lines. Functional assays demonstrated that the upregulation of miR-675 impaired cell proliferation and invasion in melanoma. Bioinformatics analysis, luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction and western blot analysis demonstrated that metadherin (MTDH) was a direct target of miR-675 in melanoma. The MTDH levels were upregulated in melanoma tissues and inversely correlated with the miR-675 expression. Furthermore, restored MTDH expression rescued the inhibition effects in melanoma cells caused by miR-675 overexpression. Thus, miR-675 may be a potential therapeutic target for melanoma. [ABSTRACT FROM AUTHOR]

Gastric cancer is the fifth most frequent malignancy and the fourth most common cause of cancer-associated mortality worldwide. MicroRNAs (miRNAs) are a group of small RNAs that regulate several cellular processes. In particular, a large number of miRNAs are involved in gastric cancer formation and progression. Thus, miRNAs may be considered as effective diagnostic biomarkers and therapeutic methods for gastric cancer. The aim of the current study was to detect miRNA (miR)-197 expression in gastric cancer and to investigate its biological role and associated mechanism in gastric cancer. In the present study, miR-197 expression was demonstrated to be considerably downregulated in gastric cancer tissues and cell lines. Its low expression level was associated with tumour size, invasive depth, tumour-node-metastasis staging and lymph node metastasis. High expression of miR-197 inhibited tumour cell proliferation and invasion in vitro. Subsequently, metadherin (MTDH) was identified as a direct target gene of miR-197 in gastric cancer, and this was confirmed by bioinformatics analysis, Dual-luciferase reporter assay, reverse transcription quantitative polymerase chain reaction and western blot analysis. MTDH expression was upregulated in gastric cancer and was inversely correlated with miR-197 expression levels. In addition, MTDH overexpression prevented the proliferation and inhibited invasion induced by miR-197 overexpression. In addition, miR-197 was demonstrated to regulate the phosphatase and tensin homolog (PTEN)/AKT signalling pathway in gastric cancer. The results of the present study suggested that miR-197 serves a tumour-suppressing role in human gastric carcinogenesis and progression by regulating the MTDH/PTEN/AKT signalling pathway. The miR-197/MTDH axis may provide a novel effective therapeutic target for patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Glioma is a well-known aggressive and malignant brain tumor, and accounts for ~30% of all brain and central nervous system tumors. A number of studies have indicated that the abnormal expression of specific microRNAs (miR) serves vital roles in the tumorigenesis and tumor development of human cancer, including glioma. miR-216b has been studied in a number of types of cancer. However, the expression pattern, molecular function and underlying mechanisms of miR-216b in glioma remain unclear. In the present study, it was demonstrated that the level of miR-216b was significantly decreased in glioma tissues and cell lines compared with matched normal tissues and primary normal human astrocytes. The reduced miR-216b expression level was correlated with the Karnofsky Performance Score and the World Health Organization grade of gliomas. Upregulation of miR-216b repressed cell proliferation and invasion in glioma. Additionally, metadherin (MTDH) was identified as a direct target gene of miR-216b in glioma. MTDH expression was demonstrated to be significantly upregulated and inversely associated with miR-216b expression in glioma specimens. MTDH knockdowns could simulate the cellular conditions induced by miR-216b overexpression in glioma cells. In addition, miR-216b regulated phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN/protein kinase B signaling pathways in glioma. These results suggested that miR-216b acted as a tumor suppressor in glioma by directly targeting MTDH and that the miR-216b/MTDH axis may be an effective therapeutic target for the treatment of patients with this disease. [ABSTRACT FROM AUTHOR]

The B-cell receptor (BCR) signaling pathway serves an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), and has been identified as a novel and effective therapeutic target of CLL, with particular focus its kinase factor, BTK. Previous studies have focused on combining the BTK inhibitor with additional chemotherapeutic agents to improve the prognosis of patients with CLL. Further investigation into the mechanism of the BTK inhibitor would promote an understanding of the pathogenesis of CLL. The current study investigated the association between ibrutinib and the Wnt signaling pathway, additionally focussing upon one of its regulators, metadherin (MTDH), which has been identified to be overexpressed in CLL and is considered a promoter of the Wnt pathway. The experiments in the current study were performed in the MEC-1 CLL cell line. Results indicated that MTDH, β-catenin and lymphoid-enhancing factor-1 were inhibited subsequent to ibrutinib treatment. The results indicate that in CLL, ibrutinib is likely to possess an inhibitory role in Wnt signaling. [ABSTRACT FROM AUTHOR]

Hepatic fibrosis is an inevitable pathological process in the progression of multiple chronic liver diseases and remains a major challenge in the treatment of liver diseases. The purpose of the present study was to demonstrate whether silencing of the long non-coding RNA LOC102553417 promoted hepatic stellate cell (HSC) apoptosis via the microRNA (miR)-30e/metadherin (MTDH) axis. A LOC102553417 silencing lentivirus was constructed and transduced into HSC-T6 cells. After confirming the silencing efficiency by reverse transcription-quantitative PCR, cell proliferation was assessed using the Cell Counting Kit-8 assay and apoptosis was assessed using flow cytometry. The interaction between LOC102553417 and miR-30e, and that between miR-30e and MTDH, was demonstrated using the dual-luciferase reporter assay and RNA binding protein immunoprecipitation. The apoptosis of HSC-T6 cells was detected after transfection of miR-30e mimics and inhibitors with or without silencing LOC102553417. Silencing of LOC102553417 curbed HSC-T6 cell proliferation and expedited their apoptosis. LOC102553417 was demonstrated to target miR-30e, whereas miR-30e targeted MTDH. In addition, LOC102553417 silencing significantly upregulated miR-30e expression levels, and significantly downregulated MTDH mRNA and protein expression levels, which resulted in a significantly reduced p-Akt/Akt ratio and significantly elevated p53 protein expression levels. Transfection with miR-30e mimic alone significantly enhanced HSC-T6 cell apoptosis and inhibits LOC102553417 and MTDH expressions, In addition, miR-30e mimic expedites the apoptosis of HSCs stimulated by LOC102553417 silencing; consistent results were obtained by reverse validation of miR-30e inhibitor. In conclusion, the present study demonstrated that LOC102553417 silencing stimulated the apoptosis of HSCs via the miR-30e/MTDH axis. [ABSTRACT FROM AUTHOR]

Metadherin (MTDH), also known as astrocyte-elevated gene-1, was first cloned in 2002 and has been confirmed as an oncogene in numerous types of cancer by previous studies. Overexpression of MTDH has been observed in multiple types of cancer, including breast, esophageal, prostate, cervical and non-small-cell lung cancer, as well as neuroblastoma and hepatocellular carcinoma. However, at present, few investigations into MTDH-associated prostate cancer have been performed. A previous study suggested that MTDH was expressed at higher levels in prostate cancer samples, compared with those of benign prostatic hyperplasia. The present study aimed to elucidate the effects of MTDH as an oncogene associated with the biological behavior of prostate cancer cells and chemotherapy-sensitivity to cisplatin in vitro. It was demonstrated that the inhibition of MTDH expression promoted cell apoptosis, reduced cell viability and weakened the invasive ability of prostate cancer cells. In addition, the suppression of MTDH expression increased cell sensitivity to cisplatin. Furthermore, it was demonstrated that MTDH-associated phosphoinositide 3-kinase/Akt signaling pathways may be involved in mediating the biological behavior of prostate cancer. [ABSTRACT FROM AUTHOR]

microRNA (miR)-22 has been reported to be downregulated in hepatocellular, lung, colorectal, ovarian and breast cancer, acting as a tumor suppressor. The present study investigated the potential effects of miR-22 on gastric cancer invasion and metastasis and the molecular mechanism. miR-22 expression was examined in tumor tissues of in 89 gastric cancer patients by in situ hybridization (ISH) analysis. Additionally, the association between miR-22 levels and clinicopathological parameters was analyzed. A luciferase assay was conducted for target identification. The ability of invasion and metastasis of gastric cancer cells in vitro and in vivo was evaluated by cell migration and invasion assays and in a xenograft model. The results showed that miR-22 was downregulated in the gastric cancer specimens and significantly correlated with the advanced clinical stage and lymph node metastasis. In addition, metadherin (MTDH) was shown to be a direct target of miR-22 and the expression of MTDH was inversely correlated with miR-22 expression in gastric cancer. Ectopic expression of miR-22 suppressed cell invasion and metastasis in vitro and in vivo. The present study suggested that miR-22 may be a valuable prognostic factor in gastric cancer. miR-22 inhibited gastric cancer cell invasion and metastasis by directly targeting MTDH. The novel miR-22/MTDH link confirmed in the present study provided a novel, potential therapeutic target for the treatment of gastric cancer. [ABSTRACT FROM AUTHOR]