4.7 Article

Long non-coding RNA MINCR aggravates colon cancer via regulating miR-708-5p-mediated Wnt/β-catenin pathway

Journal

BIOMEDICINE & PHARMACOTHERAPY
Volume 129, Issue -, Pages -

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2020.110292

Keywords

Colon cancer; MINCR; miR-708-5p; CTNNB1; Wnt/beta-catenin pathway

Funding

  1. Foundation of doctoral innovation of Shanghai Jiao Tong University School of Medicine [BXJ201733]
  2. National Natural Science Foundation of China (NSFC) [81530044]
  3. Clinical Research Plan of Shanghai Hospital Development Center (SHDC) [16CR3082B]

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Background: Increasing evidence has found that the dysregulation of long non-coding RNAs (lncRNAs) may be important indicators in tumorigenesis. MYC-induced long non-coding RNA (MINCR) has been found to be related with some cancers, such as non-small cell lung cancer and gallbladder cancer. Besides, MINCR has potentially prognostic value for colon cancer (CC) patients' prognosis, yet its function and molecular mechanism in CC are not explored. Methods: qRT-PCR evaluated gene expression, and western blot detected protein level. In vitro and in vivo experiments were adopted to understand the biological role of MINCR in CC. TOP/FOP Flash assay was performed to measure the activity of Wnt/beta-catenin pathway. RNA pull down, luciferase reporter and RIP assays were utilized to analyze the relationship among genes. Immunohistochemistry and HE staining techniques were utilized to evaluate Ki67 staining in xenografts. Results: MINCR was up-regulated in CC cells. Knockdown of MINCR suppressed cell proliferation and migration. MINCR could up-regulate CTNNB1 via sequestering miR-708-5p, resulting in activated Wnt/beta-catenin pathway. The addition of LiCl treatment, miR-708-5p inhibitor or pcDNA3.1/CTNNB1 abolished the inhibitory impacts induced by MINCR silence in CC progression. Conclusion: MINCR sponges miR-708-5p to up-regulate CTNNB1 and activate Wnt/beta-catenin pathway, thus promoting the development CC. Targeting MINCR might shed new light on the therapeutic strategies of CC.

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