Downregulation of microRNA-30d promotes cell proliferation and invasion by targeting LRH-1 in colorectal carcinoma

Yan,Likun; Qiu,Jian; Yao,Jianfeng

doi:10.3892/ijmm.2017.2958

Downregulation of microRNA-30d promotes cell proliferation and invasion by targeting LRH-1 in colorectal carcinoma

Authors:
- Likun Yan
- Jian Qiu
- Jianfeng Yao
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Affiliations: Department of General Surgery, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China
Published online on: April 20, 2017 https://doi.org/10.3892/ijmm.2017.2958
Pages: 1371-1380
Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aberrant expression of miR-30d has been reported in several types of human malignancies. However, its biological function in colorectal cancer (CRC) remains largely unknown. In this study, we identified that miR‑30d was significantly downregulated in CRC tissues compared to that observed in normal controls as detected by RT‑qPCR analysis. Downregulation of miR‑30d was significantly associated with aggressive clinicopathological parameters including tumor differentiation, invasive depth, TNM stage, lymph node metastasis, distant metastasis, and poor prognosis. Furthermore, functional analysis revealed that overexpression of miR‑30d significantly inhibited cell proliferation, caused cell cycle arrest at the G0/G1 phase, suppressed cell migration and invasion, induced cell apoptosis in vitro, and decreased tumor growth in a xenograft mouse model. Bioinformatic analysis and dual‑luciferase reporter assay revealed that liver receptor homologue‑1 (LRH‑1) is a direct target of miR‑30d in CRC cells. Rescue assay showed that LRH‑1 overexpression could restore the inhibitory effect of miR‑30d on CRC cells. In addition, miR‑30d overexpression suppressed the activation of key components of the Wnt/β‑catenin signaling pathway, β‑catenin, c‑Myc and cyclin D1, which contributed to the inhibition of CRC development. Thus, our findings suggest that miR‑30d functions as a tumor suppressor against CRC development and miR‑30d/LRH‑1/Wnt signaling may be novel potential targets for CRC treatment.

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