Hsa-miR-942 fingerprint in colorectal cancer through Wnt signaling pathway
Autor: | Sajedeh Bahonar, Romina Norouzi, Zahra Sadat Ranjbaran, Bahram M. Soltani, Shirzad Nasiri, Ali Fasihi |
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Rok vydání: | 2019 |
Předmět: |
Male
0301 basic medicine Carcinogenesis Colorectal cancer Biology medicine.disease_cause law.invention Proto-Oncogene Proteins c-myc 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation law Cell Line Tumor microRNA Genetics medicine Humans Cyclin D1 Luciferase Luciferases 3' Untranslated Regions Wnt Signaling Pathway beta Catenin Gene Expression Profiling Cell Cycle Wnt signaling pathway Computational Biology General Medicine medicine.disease Up-Regulation Gene Expression Regulation Neoplastic Blot MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis Disease Progression Cancer research Suppressor Female RNA Interference RNA Long Noncoding Colorectal Neoplasms Plasmids Signal Transduction |
Zdroj: | Gene. 712:143958 |
ISSN: | 0378-1119 |
DOI: | 10.1016/j.gene.2019.143958 |
Popis: | 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. |
Databáze: | OpenAIRE |
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