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miR-141 通过靶向 PHLPP2 表达抑制结肠癌细胞的促进增殖
Authors Fang F, Cheng L, Wu X, Ye M, Zhang H
Received 2 April 2020
Accepted for publication 28 August 2020
Published 6 November 2020 Volume 2020:12 Pages 11341—11350
DOI https://doi.org/10.2147/CMAR.S256670
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Eileen O'Reilly
Objective: Colon cancer (CC) is the third most common cancer with a high rate of incidence and mortality. Therefore, it is highly necessary to explore novel targets of CC.
Methods: The miRNA-seq and RNA-seq data of CC were accessed from the TCGA database. Differential analysis was performed using the “edgeR” package to identify differentially expressed miRNAs (DE_miRNAs). The downstream target genes of the target miRNA were then predicted by miRNA target prediction databases to identify the target mRNA. Normal colon cell line CCD-18Co and CC cell lines HCT-116, HT-29, SW620 and SW480 were chosen, and qRT-PCR was conducted to detect miR-141 expression in these cell lines. qRT-PCR and Western blot were carried out to determine PHLPP2 mRNA and protein expression, respectively. Dual-luciferase reporter gene assay was performed to verify the targeting relationship between miR-141 and PHLPP2 3ʹUTR. CCK-8 assay and colony formation assay were carried out to detect cell proliferation. Meanwhile, tumor xenograft model in nude mice was constructed to assess CC cell tumorigenic ability in vivo.
Results: miR-141 was markedly up-regulated in CC tissue. CC cell proliferation and in vivo tumorigenic ability were suppressed by miR-141 silencing but promoted by miR-141 over-expression. PHLPP2 was significantly down-regulated in cancer tissue. Dual-luciferase reporter gene assay indicated that miR-141 could bind to PHLPP2 3ʹUTR. PHLPP2 expression was noticeably elevated upon miR-141 deficiency but significantly inhibited upon miR-141 over-expression. CCK-8 and colony formation assay suggested that miR-141 facilitated CC cell proliferation by silencing PHLPP2 .
Conclusion: miR-141 promotes CC cell proliferation by targeted silencing PHLPP2 .
Keywords: miR-141 , PHLPP2 , colon cancer, proliferation