MiR-3622a-3p acts as a tumor suppressor in colorectal cancer by reducing stemness features and EMT through targeting spalt-like transcription factor 4

miR-3622a-3p通过靶向spalt样转录因子4,降低干细胞特性和EMT,从而在结直肠癌中发挥抑癌作用。

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作者:Shuchen Chang # ,Guangli Sun # ,Dan Zhang # ,Qing Li # ,Haihua Qian

Abstract

MicroRNAs are a class of small non-coding RNAs which act as oncogenes or tumor suppressors through targeting specific mRNAs. Colorectal cancer (CRC) is one of the most common malignancies worldwide. MiR-3622a-3p is found to be decreased in colorectal cancer (CRC) by analyzing data from TCGA database and there are few reports about the role of miR-3622a-3p in cancers. Our research aimed to explore the effects of miR-3622a-3p on CRC. MiR-3622a-3p was found to be down-regulated in CRC tissues and cells by qRT-PCR. The effect of miR-3622a-3p on proliferation, apoptosis, cell cycle, migration and invasion of CRC cells were investigated by a serious of biological function assays and the results revealed that miR-3622a-3p could inhibit the malignant biological properties of CRC. We performed dual luciferase assay, RNA immunoprecipitation (RIP) assay and pull-down assay to confirm the interaction between miR-3622a-3p and spalt-like transcription factor 4 (SALL4). Western blot was carried out to determine the effects of miR-3622a-3p and SALL4 on stemness features and EMT. We found that miR-3622a-3p suppressed stemness features and EMT of CRC cells by SALL4 mRNA degradation. MiR-3622a-3p could inhibit CRC cell proliferation and metastasis in vivo with tumor xenograft model and in vivo metastasis model. The CRC organoid model was constructed with fresh CRC tissues and the growth of organoids was suppressed by miR-3622a-3p. Taken together, the results of our study indicate miR-3622a-3p exerts antioncogenic role in CRC by downregulation of SALL4. The research on miR-3622a-3p might provide a new insight into treatment of CRC.

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