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

Zhou,Na; Sun,Zhao; Li,Ningning; Ge,Yuping; Zhou,Jianfeng; Han,Qin; Zhao,Lin; Bai,Chunmei

doi:10.3892/or.2018.6640

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

Authors:
- Na Zhou
- Zhao Sun
- Ningning Li
- Yuping Ge
- Jianfeng Zhou
- Qin Han
- Lin Zhao
- Chunmei Bai
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Affiliations: Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China, Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China, Institute of Basic Medical Sciences, Chinese Academy ofMedical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, P.R. China
Published online on: August 10, 2018 https://doi.org/10.3892/or.2018.6640
Pages: 2710-2721

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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.

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