MALAT1: A Promising Therapeutic Target for the Treatment of Metastatic Colorectal Cancer

Biochem Pharmacol. 2021 Aug:190:114657. doi: 10.1016/j.bcp.2021.114657. Epub 2021 Jun 16.

Abstract

Cancer metastasis research has emerged in recent years as one of the most important topics of debate in the discovery and development of novel anticancer therapies. Colorectal cancer (CRC), the third most common cancer worldwide, has a high mortality rate due to recurrence and distant metastasis to the liver. Several non-coding RNAs (ncRNAs) have been linked to metastatic CRC (mCRC), including the long non-coding RNA (lncRNA) Metastasis-Associated Lung-Adenocarcinoma Transcript 1 (MALAT1). MALAT1 is an RNA that has been linked to tumor cell proliferation, progression, epithelial-mesenchymal transition (EMT), cell migration and invasion, metastasis, and survival in mammalian species. Previously, there was no convincing evidence linking MALAT1 to mCRC. Studies have shown that MALAT1 functions as a competitive endogenous RNA (ceRNA) with microRNAs (miRNAs) and interacts directly with oncogenes and proteins. This RNA also activates several signaling pathways, including Wnt/β-catenin, PI3K/Akt/mTOR, and EMT. Meanwhile, standard chemotherapy and immunotherapy are the current treatment options for mCRC patients. However, evidence-based studies have recently demonstrated that inhibiting the MALAT1 RNA transcript can be considered as a treatment option for mCRC, highlighting the need to investigate its roles as a therapeutic target in mCRC. Thus, in this review, we looked at studies that linked MALAT1 to multiple signaling pathways implicated in mCRC, as well as its potential as a therapeutic target for the treatment of mCRC.

Keywords: Colorectal cancer; MALAT1; Signaling pathways; Therapeutic target; ceRNA.

Publication types

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

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*

Substances

  • Antineoplastic Agents
  • MALAT1 long non-coding RNA, human
  • RNA, Long Noncoding