Aberrant regulation of the LIN28A/LIN28B and let-7 loop in human malignant tumors and its effects on the hallmarks of cancer

Mol Cancer. 2015 Jun 30;14:125. doi: 10.1186/s12943-015-0402-5.

Abstract

RNA binding proteins (RBPs) and microRNAs (miRNAs) are two of the most important post-transcriptional regulators of gene expression, and their aberrant expression contributes to the development of human malignancies. Let-7, one of the most well-known tumor suppressors, is frequently down-regulated in a variety of human cancers. The RBP LIN28A/LIN28B, a direct target of the let-7 family of miRNAs, is an inhibitor of let-7 biogenesis and is frequently up-regulated in cancers. Aberrant regulation of the LIN28A/LIN28B and let-7 loop in human malignant tumors is reportedly involved in cancer development, contributing to cellular proliferation, cell death resistance, angiogenesis, metastasis, metabolism reprogramming, tumor-associated inflammation, genome instability, acquiring immortality and evading immune destruction. In this review, we summarized the mechanisms of LIN28A/LIN28B and let-7 loop aberrant regulation in human cancer and discussed the roles and potential mechanisms of the LIN28A/LIN28B and let-7 loop in regulating the hallmarks of cancer. The crosstalk between LIN28A/LIN28B and let-7 loop and certain oncogenes (such as MYC, RAS, PI3K/AKT, NF-κB and β-catenin) in regulating hallmarks of cancer has also been discussed.

Publication types

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

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Energy Metabolism
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks*
  • Genomic Instability
  • Humans
  • MicroRNAs / genetics*
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • RNA Interference
  • RNA-Binding Proteins / genetics*
  • Signal Transduction

Substances

  • LIN28B protein, human
  • MicroRNAs
  • RNA-Binding Proteins
  • mirnlet7 microRNA, human