miR-141 Promotes Colon Cancer Cell Proliferation by Targeted PHLPP2 Expression Inhibitionn

Fazhuang Fang1, Ling Cheng2, Xiaotang Wu2

  • 1Department of Hepatobiliary, Pancreatic and Gastric Surgery, Jinhua Guangfu Hospital, Jinhua 321000, People's Republic of China.

Abstract

Insights

MicroRNA-141 (miR-141) promotes colon cancer (CC) cell proliferation by targeting and silencing PH-like गर्नुहोस् protein phosphatase 2 (PHLPP2). This finding identifies a novel therapeutic target for colon cancer treatment.

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • Colon cancer (CC) is a leading cause of cancer incidence and mortality.
  • Identifying novel therapeutic targets is crucial for effective CC treatment.
  • MicroRNAs play significant roles in cancer development and progression.

Purpose of the Study:

  • To investigate the role of miR-141 in colon cancer.
  • To identify the downstream target of miR-141 involved in CC.
  • To explore the therapeutic potential of targeting the miR-141/PHLPP2 axis in CC.

Main Methods:

  • Analysis of miRNA-seq and RNA-seq data from The Cancer Genome Atlas (TCGA) database.
  • Differential expression analysis using edgeR to identify differentially expressed miRNAs (DE_miRNAs).
  • Validation of miR-141 and PHLPP2 expression in CC cell lines using qRT-PCR and Western blot.
  • Dual-luciferase reporter gene assay to confirm the targeting relationship between miR-141 and PHLPP2.
  • In vitro (CCK-8, colony formation assays) and in vivo (tumor xenograft model) experiments to assess cell proliferation and tumorigenic ability.

Main Results:

  • miR-141 was significantly upregulated in colon cancer tissues and cell lines.
  • miR-141 silencing suppressed CC cell proliferation and in vivo tumor growth, while overexpression promoted them.
  • PHLPP2 was downregulated in CC tissues, and miR-141 directly targeted and silenced PHLPP2.
  • Restoration of PHLPP2 expression inhibited miR-141-induced CC cell proliferation.

Conclusions:

  • miR-141 acts as an oncomiR in colon cancer by promoting cell proliferation.
  • The oncogenic role of miR-141 is mediated through the targeted silencing of PHLPP2.
  • The miR-141/PHLPP2 pathway represents a potential therapeutic target for colon cancer.

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