miR‑197 promotes the invasion and migration of colorectal cancer by targeting insulin‑like growth factor‑binding protein�3

Abstract

The incidence and mortality of colorectal cancer (CRC) have been rising rapidly in China. A number of miRNAs have been confirmed to be involved in diverse biological processes of CRC. However, whether miR‑197 plays a role in migration and invasion of CRC has never been explored. In the present study Transwell chambers were used in in vitro migration and invasion assays. Dual-luciferase reporter assay was employed to confirm the target of miR‑197. RT‑PCR and IHC staining were performed to quantify miR‑197 and IGFBP3 expression, respectively. Clinicopathological features were collected for statistical analysis. We observed that the overexpression of miR‑197 significantly promoted migration and invasion in 3 CRC cell lines including HCT8, HCT116 and SW480 (P<0.05), while the inhibition of miR‑197 weakened both biological processes (P<0.05). In bioinformatics and dual-luciferase reporter assay, luciferase activities of IGFBP3‑WT‑transfected cells significantly decreased upon miR‑197 overexpression and this inhibitory effect was abolished when miR‑197 binding region in IGFBP3 3'‑UTR was mutated, which indicated that miR‑197 directly suppressed the expression of IGFBP3 in CRC cells by targeting its 3'UTR. Downregulation of the expression of IGFBP3 by using targeted siRNA led to significant enhancement of cell migration and invasion in two CRC cell lines including HCT8 and HCT116 (P<0.05). Finally, in cancerous tissues of CRC patients, the miR‑197 level was inversely correlated with the expression of IGFBP3 (P=0.026), which indicated that miR‑197 may modulate cell migration and invasion by targeting IGFBP3 in CRC patients. In conclusion, we revealed that miR‑197 modulates IGFBP3 and therefore plays a critical role in regulating CRC migration and invasion.

Genomics and prognosis analysis of epithelial-mesenchymal transition in colorectal cancer patients

“…Of note, contrary to our research, Zhou et al confirmed that decreased expression of IGFBP3 promoted tumor metastasis in CRC [ 34 ]. Another study indicated that silencing IGFBP3 in two human CRC cell lines, SW480 and Caco2, could reduce the proliferation, colony formation, and migration.…”

Identifying a ten-microRNA signature as a superior prognosis biomarker in colon adenocarcinoma

“…Therefore, in this study, we identified a ten-microRNA signature to better predict the prognosis of COAD patients. Among those selected microRNAs, seven of them (hsa-miR-32, hsa-miR-197, hsa-miR-210, hsa-miR-3189, hsa-miR-3917, hsa-miR-4999, and hsa-miR-6854) were previous reported to have critical roles in colorectal carcinoma [13][14][15][16]. Three of them (hsa-miR-3189, hsa-miR-3917 and hsa-miR-6854) appear to be protective factors for colon cancer consistent with previous study and four of them (hsa-miR-32, hsa-miR-197, hsa-miR-210 and hsa-miR-4999) display to be risky factors for colon cancer also consistent with previous study.…”

The Interplay Between Non-coding RNAs and Insulin-Like Growth Factor Signaling in the Pathogenesis of Neoplasia

“…In colorectal cancer cells, the oncogenic protein IGF2BP2 has a functional interaction with miR-195 through which it regulates RAF1 expression and participates in the carcinogenic process (Ye S. et al, 2016). Meanwhile, miR-197 can inhibit the expression of IGFBP3 through binding with its 3 -UTR, hence enhancing cell migratory potential and invasion of colorectal cancer cells (Zhou et al, 2018). Supplementary Table 1 reviews the results of studies that displayed the role of IGF-associated miRNAs in the neoplastic conditions.…”