LncRNA RP11-295G20.2 regulates hepatocellular carcinoma cell growth and autophagy by targeting PTEN to lysosomal

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Linhui Liang1, Lin Huan1, Jiajia Wang1

  • 1Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

Cell Discovery
|December 14, 2021
PubMed

Insights

A novel long non-coding RNA, RP11-295G20.2, drives liver cancer by degrading the PTEN tumor suppressor protein via the lysosome. This discovery reveals a new mechanism for PTEN loss in cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • PTEN protein is a critical tumor suppressor frequently lost in various cancers.
  • The molecular mechanisms underlying PTEN loss, particularly the role of long non-coding RNAs (lncRNAs), remain poorly understood in hepatocellular carcinoma (HCC).

Purpose of the Study:

  • To investigate the role of lncRNA RP11-295G20.2 in hepatocellular carcinoma (HCC).
  • To elucidate the molecular mechanism by which RP11-295G20.2 influences PTEN protein levels and function in liver cancer.

Main Methods:

  • Quantitative analysis of RP11-295G20.2 expression in HCC tissues and cell lines.
  • In vitro and in vivo assays to assess the functional impact of RP11-295G20.2 on cancer cell growth and autophagy.
  • Biochemical assays to determine the interaction between RP11-295G20.2 and PTEN protein.
  • Analysis of PTEN degradation pathways (lysosomal vs. proteasomal).
  • Correlation analysis between RP11-295G20.2 and PTEN expression in patient samples (TCGA/TCPA-LIHC).

Main Results:

  • RP11-295G20.2 is significantly upregulated in HCC and promotes liver cancer cell proliferation.
  • RP11-295G20.2 inhibits autophagy in liver cancer cells.
  • RP11-295G20.2 directly binds to PTEN protein, leading to its degradation via the lysosomal pathway.
  • Expression of RP11-295G20.2 is inversely correlated with PTEN protein levels in HCC patient samples.
  • RP11-295G20.2 influences AKT phosphorylation and FOXO3a nuclear translocation, affecting autophagy-related gene transcription.

Conclusions:

  • The lncRNA RP11-295G20.2 acts as an oncogene in HCC by directly targeting PTEN for lysosomal degradation.
  • This RP11-295G20.2/PTEN axis represents a novel molecular mechanism contributing to PTEN loss in liver cancer.
  • Targeting this axis may offer new therapeutic strategies for HCC patients.

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