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PI3K/AKT/mTOR pathway-related long non-coding RNAs: roles and mechanisms in hepatocellular carcinoma

Yuting Wu1, Yingshi Zhang1, Xiaochun Qin1

  • 1Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.

Pharmacological Research
|September 11, 2020
PubMed

Insights

Long non-coding RNAs (lncRNAs) are newly identified regulators of the PI3K/AKT/mTOR pathway in hepatocellular carcinoma (HCC). This review details 67 lncRNAs impacting HCC development and prognosis, offering potential diagnostic and therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Hepatocellular carcinoma (HCC) is a prevalent and lethal malignancy.
  • The phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is frequently dysregulated in HCC pathogenesis.
  • The precise mechanisms of PI3K/AKT/mTOR pathway activation in HCC remain incompletely understood.

Purpose of the Study:

  • To review and summarize the functional roles of long non-coding RNAs (lncRNAs) in the PI3K/AKT/mTOR signaling axis in hepatocellular carcinoma.
  • To elucidate the involvement of lncRNAs in hepatocarcinogenesis via PI3K/AKT/mTOR pathway regulation.
  • To identify potential diagnostic and therapeutic targets for HCC based on lncRNA dysregulation.

Main Methods:

  • Comprehensive literature review of studies investigating lncRNAs and the PI3K/AKT/mTOR pathway in HCC.
  • Analysis of reported oncogenic or anti-oncogenic effects of lncRNAs.
  • Examination of lncRNA regulation at epigenetic, transcriptional, and post-transcriptional levels.
  • Correlation analysis of lncRNAs with HCC clinicopathological features and prognosis.

Main Results:

  • Identified and summarized 67 dysregulated PI3K/AKT/mTOR pathway-related lncRNAs in HCC.
  • Demonstrated that these lncRNAs exert oncogenic or anti-oncogenic effects through various regulatory mechanisms.
  • Highlighted the involvement of these lncRNAs in critical HCC biological processes including proliferation, metastasis, drug resistance, radio-resistance, energy metabolism, and autophagy.
  • Observed associations between many dysregulated lncRNAs and HCC clinicopathological features and patient prognosis.

Conclusions:

  • lncRNAs represent a significant new dimension in understanding hepatocarcinogenesis through PI3K/AKT/mTOR pathway dysregulation.
  • Dysregulated lncRNAs play pivotal roles in HCC initiation and progression.
  • These lncRNAs hold promise as potential biomarkers for HCC diagnosis and therapeutic targets.
Keywords:
5-fluorouracil (PubChem CID3385)Capecitabine (PubChem CID60953)Doxorubicin (PubChem CID31703)Drug resistanceGemcitabine (PubChem CID60750)Lenvatinib (PubChem CID9823820)MetastasisOncogenicPhosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathwayPost-transcriptional regulationPrognosisRetinoic acid (PubChem CID444795)Sorafenib (PubChem CID216239)Sunitinib (PubChem CID5329102)Trichostatin (PubChem CID444732)

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