Hsa-miR-942 fingerprint in colorectal cancer through Wnt signaling pathway

• Published in: Gene Vol. 712; p. 143958
• Main Authors: Fasihi, Ali, Soltani, Bahram M., Ranjbaran, Zahra Sadat, Bahonar, Sajedeh, Norouzi, Romina, Nasiri, Shirzad
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05-09-2019
• Subjects: Cell cycle; CRC; hsa-miR-942; Wnt signaling; GSK3β; Wnt signaling; APC; CRC; Cell cycle; CK1; miR-942; hsa-miR-942
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2019.143958

The Wnt signaling pathway has been identified for its function in carcinogenesis and embryonic development. It is known to play a vital role in the initiation and development of colorectal cancer (CRC). Therefore, it is of great importance for CRC research to illuminate the mechanisms which regulate Wnt pathway activity. Here, we intended to examine the effect of hsa-miR-942 (miR-942) on the Wnt signaling activity, cell cycle progression, and its expression in CRC tissues. RT-qPCR results indicated that miR-942 is significantly upregulated in colorectal cancer. Then, overexpression of miR-942 promoted, whereas its inhibition decreased the Wnt signaling activity, detected by RT-qPCR and Top/Fop flash assay. Inhibition of Wnt signaling by using PNU-74654 or IWP-2 small molecules indicated that miR-942 applies its effect to the β-catenin degradation complex level. Then, RT-qPCR and dual luciferase assay showed that miR-942 upregulated Wnt signaling through direct targeting of APC, which is a tumor suppressor in Wnt signaling pathway. Furthermore, the western blotting analysis indicated that β.catenin, as a main member of Wnt signaling pathway is upregulated following the overexpression of miR-942. Finally, miR-942 overexpression resulted in cell cycle progression in SW480 cells. Taken together, our findings established an oncogenic role for miR-942 in CRC and indicated that this miRNA might be a crucial target for CRC therapy.
•miR-942 is significantly upregulated in colorectal cancer.•miR-942 is an onco-miR affecting Wnt signaling through direct targeting of APC.•β.catenin and WNT3a are upregulated following the overexpression of miR-942.•Overexpression of miR-942 caused higher expression of c-myc and cyclin D1.•miR-942 might be a crucial target for CRC therapy.