MicroRNA‐143‐3p inhibits colorectal cancer metastases by targeting ITGA6 and ASAP3

Abstract

MicroRNAs, which regulate mRNAs, operate through a variety of signaling pathways to participate in the development of colorectal cancer (CRC). In this study, we found that microRNA (miR)‐143‐3p expression was significantly lower in both CRC and liver metastatic CRC tissues from liver compared with normal colonic tissues. Functional assays showed that miR‐143‐3p inhibited CRC cell invasion and migration in vitro. Using a bioinformatics approach, we identified miR‐143‐3p target mRNAs. Among the candidate targets, only the expression of integrin alpha 6 (ITGA6) and ArfGAP with the SH3 domain and ankyrin repeat and PH domain 3 (ASAP3) were significantly reduced by miR‐143‐3p mimics as examined by western blot, and the metastasis potential of CRC cells was attenuated by endogenous ITGA6 and ASAP3 knockdown, determined by migration and invasion assays. Both ITGA6 and ASAP3 were upregulated in CRC tissues compared to normal tissues. Analysis of the relationship between clinicopathological features and ITGA6/ASAP3 protein expression in 200 patients with CRC showed a significant difference in positive ITGA6 expression between the early stage (I + II) and the advanced stage (III + IV), and ASAP3 expression levels positively correlated with metastasis in the lymph nodes. These results indicate that miR‐143‐3p acts as an anti‐oncogene by downregulating ITGA6/ASAP3 protein expression and could offer new insight into potential therapeutic targets for CRC.

Hsa_circ_0003998 promotes epithelial to mesenchymal transition of hepatocellular carcinoma by sponging miR-143-3p and PCBP1

“…Student's t-test was used. *p < 0.05, **p < 0.01, ***p < 0.001 invasion, and metastasis in multiple cancers [26][27][28] as well as the inhibitor of the EMT-related genes [29][30][31]. Furthermore, there was no significant correlation between the expression of miR-143-3p and circ0003998.…”

A Triple-Regulated Oncolytic Adenovirus Carrying MicroRNA-143 Exhibits Potent Antitumor Efficacy in Colorectal Cancer

“…We found that the expression of miRNA-143 in CRC tissues was lower than in adjacent normal tissues, which was in agreement with previous reports. [8][9][10] In MTT assays, the proliferative ability of HCT116, RKO, SW480, and LoVo cells was greater inhibited by overexpression of miR-143. The results of flow-cytometric analysis revealed that overexpression of miR-143 in HCT116 and SW480 could induce cellular apoptosis.…”

“…7 MiR-143 which is downregulated in CRC tissues, are involved in the regulation of several cellular processes including proliferation, migration and chemoresistance. [8][9][10] Furthermore, Guo et al 8 found that the expression of miR-143 has significantly decreased in liver metastatic CRC tissues compared with primary CRC tissues and that overexpression of miR-143 showed the inhibitory effect on the migration and invasion potential of CRC cells in vivo. The overexpression of miR-143 in experimental cancer models appeared to be beneficial as a potential cancer therapy.…”

MicroRNA‑628‑5p inhibits cell proliferation and induces apoptosis in colorectal cancer through downregulating CCND1 expression levels

“…Some mirnas also exhibit low expression levels in colorectal cancer tissues; the significant downregulation of mir-4262 expression levels in colorectal cancer tissue promotes apoptosis and inhibits the proliferation of colorectal cancer cells (40). in addition, low expression levels of mirnas in colorectal cancer tissues have also been detected (41); in one study, miR-144 expression levels were significantly lower in colon cancer in vivo and in vitro (42), whereas in another, mir-143-3p expression levels were observed to be decreased in colorectal cancer (43). The present study revealed that the expression level of miR-628-5p was significantly decreased in colorectal cancer tissues and cell lines compared with primary tissues and normal cells.…”