The role of Lin28A and Lin28B in cancer beyond Let-7

FEBS Lett. 2024 Dec;598(24):2963-2979. doi: 10.1002/1873-3468.15004. Epub 2024 Aug 16.

Abstract

Lin28A and Lin28B are paralogous RNA-binding proteins that play fundamental roles in development and cancer by regulating the microRNA family of tumor suppressor Let-7. Although Lin28A and Lin28B share some functional similarities with Let-7 inhibitors, they also have distinct expression patterns and biological functions. Increasing evidence indicates that Lin28A and Lin28B differentially impact cancer stem cell properties, epithelial-mesenchymal transition, metabolic reprogramming, and other hallmarks of cancer. Therefore, it is important to understand the overexpression of Lin28A and Lin28B paralogs in specific cancer contexts. In this review, we summarize the main similarities and differences between Lin28A and Lin28B, their implications in different cellular processes, and their role in different types of cancer. In addition, we provide evidence of other specific targets of each lin28 paralog, as well as the lncRNAs and miRNAs that promote or inhibit its expression, and how this impacts cancer development and progression.

Keywords: IncRNA; Lin28A; Lin28B; cancer; let‐7; overexpression; siRNA.

Publication types

  • Review

MeSH terms

  • Animals
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neoplasms* / genetics
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism

Substances

  • RNA-Binding Proteins
  • MicroRNAs
  • Lin28A protein, human
  • LIN28B protein, human
  • mirnlet7 microRNA, human
  • RNA, Long Noncoding