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.
Highlights
Colorectal cancer (CRC) remains to be one of the most common malignancies all over the world[1]
The differentially expressed mortality of CRC ranked the fourthMicroRNAs (miRNAs) were shown in the volcano plot (Fig. 1a). 141 miRNAs were up-regulated in CRC (Log[2] FC > 2, p < 0.05) while 171miRNAs were downregulated in CRC (Log[2] FC < −2, p < 0.05)
The 80 CRC patients were divided into high group and low group based on miR3622a-3p expression
Summary
Colorectal cancer (CRC) remains to be one of the most common malignancies all over the world[1]. MicroRNAs (miRNAs) are a class of small non-coding RNAs which consist of 20–24 nucleotides and can regulate expression of targeted genes by binding to their 3′untranslational regions (3′-UTR)[6,7]. MiRNAs have been demonstrated to play a promotive or inhibitory role in Official journal of the Cell Death Differentiation Association. Chang et al Cell Death and Disease (2020)11:592 many types of tumors[8]. MiR-3622a-3p has been reported to promote development of bladder cancer by targeting LASS29. It has been reported that miR-3622a-3p could suppress prostate cancer progression by inhibiting epithelial–mesenchymal transition (EMT)[10]. The effect of miR-3622a-3p on CRC has not been elucidated so far
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