Targeting Autophagy Using Long Non-Coding RNAs (LncRNAs): New Landscapes in the Arena of Cancer Therapeutics

Cells. 2023 Mar 6;12(5):810. doi: 10.3390/cells12050810.

Abstract

Cancer has become a global health hazard accounting for 10 million deaths in the year 2020. Although different treatment approaches have increased patient overall survival, treatment for advanced stages still suffers from poor clinical outcomes. The ever-increasing prevalence of cancer has led to a reanalysis of cellular and molecular events in the hope to identify and develop a cure for this multigenic disease. Autophagy, an evolutionary conserved catabolic process, eliminates protein aggregates and damaged organelles to maintain cellular homeostasis. Accumulating evidence has implicated the deregulation of autophagic pathways to be associated with various hallmarks of cancer. Autophagy exhibits both tumor-promoting and suppressive effects based on the tumor stage and grades. Majorly, it maintains the cancer microenvironment homeostasis by promoting viability and nutrient recycling under hypoxic and nutrient-deprived conditions. Recent investigations have discovered long non-coding RNAs (lncRNAs) as master regulators of autophagic gene expression. lncRNAs, by sequestering autophagy-related microRNAs, have been known to modulate various hallmarks of cancer, such as survival, proliferation, EMT, migration, invasion, angiogenesis, and metastasis. This review delineates the mechanistic role of various lncRNAs involved in modulating autophagy and their related proteins in different cancers.

Keywords: autophagy; cancer; lncRNAs; therapeutics.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / genetics
  • Homeostasis
  • Humans
  • MicroRNAs* / genetics
  • Neoplasms* / pathology
  • RNA, Long Noncoding* / genetics
  • Tumor Microenvironment

Substances

  • RNA, Long Noncoding
  • MicroRNAs

Grants and funding

This work was supported by a DAICENTER grant awarded to Prof. Ajaikumar B. Kunnumakkara, by the Department of Biotechnology (DBT), Government of India. This work was supported by Singapore Ministry of Education Tier 1 grant to Dr. Gautam Sethi. The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University (KKU) for funding this work through the Research Group Program under the Grant Number: (R.G.P.1/224/43).