Downregulation of microR-147b represses the proliferation and invasion of thyroid carcinoma cells by inhibiting Wnt/β-catenin signaling via targeting SOX15.

microRNA-147b (miR-147b) is a newly identified tumor-related miRNA that is dysregulated in multiple cancer types. Yet, the role of miR-147b in thyroid carcinoma remains unknown. Herein, we found that miR-147b expression was upregulated in thyroid carcinoma tissues and cell lines. miR-147b inhibition decreased the proliferation, colony formation, and invasion of thyroid carcinoma cells. The tumor suppressive gene SRY-related high-mobility-group box gene 15 (SOX15) was predicted as a miR-147b target gene. SOX15 expression was markedly decreased in thyroid carcinoma tissues and inversely correlated with the miR-147b expression. SOX15 overexpression repressed the proliferation and invasion of thyroid carcinoma cells associated with downregulation of Wnt/β-catenin signaling. SOX15 knockdown abolished the miR-147b-inhibition-mediated antitumor effect. miR-147b inhibition or SOX15 overexpression retarded the tumor growth of thyroid carcinoma cells in vivo. Overall, our study suggests that miR-147b inhibition restrains the proliferation and invasion of thyroid carcinoma cells through upregulation of SOX15 and inhibition of Wnt/β-catenin signaling.

Xu C ，Liu J ，Yao X ，Bai Y ，Zhao Q ，Zhao R ，Kou B ，Li H ，Han P ，Wang X ，Guo L ，Zheng Z ，Zhang S ... -  《-》

SOX15 exerts antitumor function in glioma by inhibiting cell proliferation and invasion via downregulation of Wnt/β-catenin signaling.

Sex-determining region of Y chromosome-related high-mobility-group box 15 (SOX15) has recently emerged as a candidate tumor-inhibitor in multiple types of human tumors. To date, the involvement of SOX15 in glioma is undetermined. The purpose of this study was to investigate the expression, function and potential molecular mechanism of SOX15 in glioma. Relative mRNA expression was analyzed by real-time quantitative PCR. Protein expression was determined by Western blot. Cell proliferation was assessed by cell counting kit-8 and colony formation assay. Cell invasion was evaluated by Matrigel invasion assay. Wnt/β-catenin activation was monitored by luciferase reporter assay. SOX15 expression was decreased in glioma tissues and cell lines compared with normal controls. Kaplan-Meier analysis revealed that patients with low expression of SOX15 had shorter survival than those who had high expression of SOX15. The upregulation of SOX15 markedly repressed the proliferation and invasion of glioma cells, whereas its depletion enhanced glioma cell proliferation and invasion. Research into the mechanism revealed that SOX15 exerted an inhibitory effect on Wnt/β-catenin signaling in glioma cells. Notably, overexpression of β-catenin partially reversed the SOX15 overexpression-mediated tumor-suppressive effect. In addition, SOX15 overexpression significantly impeded tumor formation by glioma cells in vivo in a mouse xenograft model associated with downregulation of active β-catenin expression. These data demonstrate that SOX15 functions as a potential tumor-suppressor in glioma by inhibiting cell proliferation and invasion via the downregulation of Wnt/β-catenin signaling.

Zhang D ，Guo S ，Wang H ，Hu Y ... -  《-》

SOX30, a target gene of miR-653-5p, represses the proliferation and invasion of prostate cancer cells through inhibition of Wnt/β-catenin signaling.

Sex-determining region Y-box containing gene 30 (SOX30) is a newly identified tumor-associated gene in several types of cancer. However, whether SOX30 is involved in the development and progression of prostate cancer remains unknown. This study investigated the potential role of SOX30 in prostate cancer. Prostate cancer cell lines and a normal prostate epithelial cell line were used for the experiments. The expression of SOX30 was determined using quantitative real-time PCR and western blot analysis. The malignant cellular behaviors of prostate cancer were assessed using the Cell Counting Kit-8, colony formation and Matrigel invasion assays. The miRNA-mRNA interaction was validated using the dual-luciferase reporter assay. SOX30 expression was lower in cells of prostate cancer lines than in cells of the normal prostate epithelial line. Its overexpression repressed the proliferation and invasion of prostate cancer cells. SOX30 was identified as a target gene of microRNA-653-5p (miR-653-5p), which is upregulated in prostate cancer tissues. MiR-653-5p overexpression decreased SOX30 expression, while its inhibition increased SOX30 expression in prostate cancer cells. MiR-653-5p inhibition also markedly restricted prostate cancer cell proliferation and invasion. SOX30 overexpression or miR-653-5p inhibition significantly reduced β-catenin expression and downregulated the activation of Wnt/β-catenin signaling. SOX30 knockdown significantly reversed the miR-653-5p inhibition-mediated inhibitory effect on the proliferation, invasion and Wnt/β-catenin signaling in prostate cancer cells. These results reveal a tumor suppressive function for SOX30 in prostate cancer and confirmed the gene as a target of miR-653-5p. SOX30 upregulation due to miR-653-5p inhibition restricted the proliferation and invasion of prostate cancer cells, and this was associated with Wnt/β-catenin signaling suppression. These findings highlight the importance of the miR-653-5p-SOX30-Wnt/β-catenin signaling axis in prostate cancer progression.

Fu Q ，Sun Z ，Yang F ，Mao T ，Gao Y ，Wang H ... -  《-》

Capn4 expression is modulated by microRNA-520b and exerts an oncogenic role in prostate cancer cells by promoting Wnt/β-catenin signaling.

Accumulating evidence reports that Capn4 plays an important role in the development and progression of various malignant cancers. However, whether Capn4 is involved in prostate cancer remains unclear. Therefore, the aim of this study was to investigate the expression, biological function and regulatory mechanism of Capn4 in prostate cancer. Herein, we found that Capn4 was highly expressed in prostate cancer cell lines compared with normal prostate cells. Capn4 gene silencing markedly suppressed the growth, invasion and Wnt/β-catenin signaling of prostate cancer cells, whereas Capn4 overexpression showed an oncogenic effect. Moreover, silencing of β-catenin significantly blocked the oncogenic effect of Capn4 overexpression. Bioinformatics analysis predicted that Capn4 was a potential target gene of microRNA-520b (miR-520b), which has been reported as a tumor suppressive miRNA in various cancers. The dual-luciferase reporter assay confirmed that miR-520b directly bound to the 3'-untranslated region of Capn4. Real-time quantitative PCR and Western blot analysis showed that miR-520b negatively regulated Capn4 expression in prostate cancer cells in vitro. Furthermore, we found that miR-520b was significantly downregulated in prostate cancer cell lines and tissues. In addition, miR-520b expression was inversely correlated with Capn4 expression in prostate cancer clinical specimens. Overexpression of miR-520b mimicked the tumor suppressive effect of Capn4 siRNA, whereas inhibition of miR-520b had an oncogenic effect. Restoration of Capn4 significantly blocked the antitumor effect of miR-520b in prostate cancer cells. Overall, our findings demonstrate an oncogenic role of Capn4 in prostate cancer and show that its expression is epigenetically regulated by miR-520b. Our results reveal that suppression of Capn4 by miR-520b inhibits the growth and invasion of prostate cancer cells associated with downregulated Wnt/β-catenin signaling, indicating an important role of the miR-520b/Capn4/Wnt/β-catenin regulation axis in the molecular pathogenesis of prostate cancer. Our study suggests that miR-520b and Capn4 may represent potential and novel therapeutic targets for prostate cancer.

Ren W ，Wang D ，Li C ，Shu T ，Zhang W ，Fu X ... -  《-》

MicroRNA-506 inhibits tumor growth and metastasis in nasopharyngeal carcinoma through the inactivation of the Wnt/β-catenin signaling pathway by down-regulating LHX2.

Liang TS ，Zheng YJ ，Wang J ，Zhao JY ，Yang DK ，Liu ZS ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》