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LincRNA-p21 activates endoplasmic reticulum stress and inhibits hepatocellular carcinoma

Ning Yang1, Yong Fu1, Haibin Zhang1

  • 1Hepatobiliary Surgery Department V, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

Oncotarget
|August 26, 2015
PubMed

Insights

Long non-coding RNA p21 (lincRNA-p21) acts as a tumor suppressor in hepatocellular carcinoma. Its downregulation correlates with advanced disease and poor survival, while its restoration inhibits cancer growth and enhances treatment response by promoting ER stress and apoptosis.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • LincRNA-p21, a downstream transcript of p53, regulates gene expression and is involved in various cellular processes.
  • The specific role of lincRNA-p21 in human hepatocellular carcinoma (HCC) has not been fully elucidated.

Purpose of the Study:

  • To investigate the function and mechanism of lincRNA-p21 in human hepatocellular carcinoma.
  • To determine if lincRNA-p21 can serve as a prognostic marker or therapeutic target for HCC.

Main Methods:

  • Analysis of lincRNA-p21 expression in HCC tissues and correlation with clinical parameters.
  • In vitro studies involving lincRNA-p21 knockdown and overexpression in HCC cell lines (HepG2, Huh7, Bel-7042).
  • In vivo tumor xenograft experiments and mechanistic studies focusing on ER stress and apoptosis.

Main Results:

  • LincRNA-p21 expression was downregulated in HCC tissues and associated with advanced stage and poor prognosis.
  • LincRNA-p21 knockdown promoted HCC cell proliferation and colony formation in vitro.
  • LincRNA-p21 overexpression inhibited HCC cell growth in vivo and sensitized cells to sorafenib treatment, partly through ER stress induction and enhanced apoptosis.

Conclusions:

  • LincRNA-p21 functions as a tumor-suppressive lncRNA in human hepatocellular carcinoma.
  • LincRNA-p21's tumor-suppressive effects are mediated by the promotion of ER stress, leading to apoptosis.
  • LincRNA-p21 represents a potential prognostic biomarker and therapeutic target for HCC.
Keywords:
ER stresshepatocellular carcinomalincRNA-p21sorafenib

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