MicroRNA-147b suppresses the proliferation and invasion of non-small-cell lung cancer cells through downregulation of Wnt/β-catenin signalling via targeting of RPS15A.

Deregulation of microRNAs (miRNAs) leads to malignant growth and aggressive invasion during cancer occurrence and progression. miR-147b has emerged as one of the cancer-related miRNAs that are dysregulated in multiple cancers. Yet, the relevance of miR-147b in non-small-cell lung cancer (NSCLC) remains unclear. In the present study, we aimed to report the biological function and signalling pathways mediated by miR-147b in NSCLC. Our results demonstrate that miR-147b expression is significantly downregulated in NSCLC tissues and cell lines. Overexpression of miR-147b decreased the proliferative ability, colony-forming capability, and invasive potential of NSCLC cells. Notably, our study identified ribosomal protein S15A (RPS15A), an oncogene in NSCLC, as a target gene of miR-147b. Our results showed that miR-147b negatively modulates RPS15A expression in NSCLC cells. An inverse correlation between miR-147b and RPS15A was evidenced in NSCLC specimens. Moreover, miR-147b overexpression downregulated the activation of Wnt/β-catenin signalling via targeting of RPS15A. Overexpression of RPS15A partially reversed the miR-147b-mediated antitumour effect in NSCLC cells. Collectively, these findings reveal that miR-147b restricts the proliferation and invasion of NSCLC cells by inhibiting RPS15A-induced Wnt/β-catenin signalling and suggest that the miR-147b/RPS15A/Wnt/β-catenin axis is an important regulatory mechanism for malignant progression of NSCLC.

Ning Q ，Pang Y ，Shao S ，Luo M ，Zhao L ，Hu T ，Zhao X ... -  《-》

Overexpression of microRNA-519d-3p suppressed the growth of pancreatic cancer cells by inhibiting ribosomal protein S15A-mediated Wnt/β-catenin signaling.

Ribosomal protein S15A (RPS15A) has emerged as a novel oncogene of various human cancers. However, whether RPS15A is involved in pancreatic cancer remains unclear. In this study, we aimed to investigate the potential relevance of RPS15A in pancreatic cancer and elucidate the underlying regulatory mechanism. We found that RPS15A expression was significantly up-regulated in pancreatic cancer cell lines. RPS15A knockdown resulted in a decrease of cell proliferation and colony formation, and induced cell cycle arrest in G0/G1 phases of pancreatic cancer cells in vitro. In addition, RPS15A knockdown down-regulated β-catenin expression and blocked the activation of Wnt signaling. Notably, RPS15A was identified as a target gene of microRNA-519d-3p (miR-519d-3p), a tumor suppressive miRNA. Further data showed that miR-519d-3p negatively regulated RPS15A expression in pancreatic cancer cells. Moreover, miR-591d-3p expression was significantly decreased in pancreatic cancer cell lines and tissues and was inversely correlated with RPS15A expression. The overexpression of miR-519d-3p significantly inhibited the proliferation and Wnt/β-catenin signaling in pancreatic cancer cells, mimicking the similar effect of RPS15A knockdown. However, restoration of RPS15A expression partially reversed the antitumor effect of miR-519d-3p. Taken together, our results demonstrate that RPS15A knockdown or RPS15A inhibition by miR-519d-3p suppresses the growth of pancreatic cancer cells associated with the inhibition of Wnt/β-catenin signaling. Our study suggests that the miR-519d-3p/RPS15A/Wnt/β-catenin regulation axis plays an important role in the progression of pancreatic cancer and may serve as potential targets for treatment of pancreatic cancer.

Liang J ，Liu Y ，Zhang L ，Tan J ，Li E ，Li F ... -  《-》

MicroRNA-147b induces neuroendocrine differentiation of prostate cancer cells by targeting ribosomal protein RPS15A.

Prostate cancer (PCa) is the leading cause of cancer related deaths in men, often androgen deprivation therapy (ADT) leads to the progression of androgen independent PCa (AIPC) which further leads to Neuroendocrine PCa (NEPC). Identifying the molecular mechanisms which navigate the neuroendocrine differentiation (NED) of PCa cells is clinically relevant. It has been suggested that the micro RNAs (miRNAs) play an important role in the regulation of intrinsic mechanisms relevant to tumor progression, resistance as a result leads to poor prognosis. miR-147b has been transpiring as one of the deregulated miRNAs associated with the occurrence of multiple cancers. The present study has studied the role of miRNA-147b in inducing NEPC. To investigate the functional role of miR-147b in NEPC, we have expressed miRNA mimics or inhibitors in PCa cells and monitored the progression of NEPC along with PCa cell proliferation and survival. The molecular mechanism miRNA-147b follows was studied using western blot and reverse transcription polymerase chain analysis. miRNA target prediction using bioinformatics tools followed by target validation using luciferase reporter assays was performed. In the present study, we found that miR-147b is highly expressed in AIPC cell lines in particular neuroendocrine cells NCI-H660 and NE-LNCaP derived from LNCaP. Mechanistic studies revealed that overexpression of miR-147b or miRNA mimics induced NED in LNCaP cells in in-vitro while its inhibitor reversed the NE features (increased NE markers and reduced prostate specific antigen) of PC3, NCI-H660 and NE-LNCaP cells. In addition, miR-147b reduced the proliferation rate of LNCaP cells via elevated p27kip1 and lowered cyclin D1 for promoting differentiation. In reporter assays, we have identified ribosomal protein S15A (RPS15A) is a direct target of miRNA-147b and RPS15A expression was negatively regulated by miR-147b in PCa cells. Furthermore, we also report that RPS15A is downregulated in NEPC cells and its expression is inversely correlated with NE markers. Targeting the miR-147b - RPS15A axis may overcome the progression of NEPC and serve as a novel therapeutic target to attenuate NED progression of PCa.

Natani S ，Ramakrishna M ，Nallavolu T ，Ummanni R ... -  《-》

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 ... -  《-》

MiR-770 inhibits tumorigenesis and EMT by targeting JMJD6 and regulating WNT/β-catenin pathway in non-small cell lung cancer.

MicroRNAs (miRNAs) plays important role in development and disease, especially in cancer including non-small cell lung cancer (NSCLC). However, the role of miR-770 in NSCLC remains unclear. In this study, we aimed to study the function and mechanism of miR-770 in tumorigenesis of NSCLC. RT-qPCR was used to measure the expression levels of miR-770 in NSCLC tissues and cells. MTT assay, colony formation assay, flow cytometric analysis and transwell migration and invasion assays were performed to investigate the role of miR-770 in NSCLC cells. Bioinformatics and luciferase reporter analyses were used to demonstrate that whether the Jumonji domain-containing 6 (JMJD6) as a direct target of miR-770. The function of JMJD6 in NSCLC was also investigated. Finally, in vivo animal experiment was used to study whether miR-770 was capable of inhibiting tumor growth by inhibiting JMJD6. We first showed that miR-770 was downregulated in NSCLC tissues and cell lines, and the low expression of miR-770 was correlated with poor patient survival in NSCLC patients. miR-770 acted on a tumor suppressor by binding to the 3'UTR of JMJD6 and downregulated its expression in NSCLC cells. This study also demonstrated that JMJD6 played as an oncogene in NSCLC cells. miR-770 overexpression was capable of inhibiting NSCLC tumor growth by inhibiting JMJD6 and its downstream WNT/β-catenin pathway both in vitro and in vivo. The present study indicated that miR-770 functioned as a tumor suppressor and it might be a potential biomarker and therapeutic target in NSCLC.

Zhang Z ，Yang Y ，Zhang X 《-》