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Tanshinone T1/T2A inhibits non-small cell lung cancer through Lin28B-let-7-BORA/MYC regulatory network

Yanli Li1, Ziyi Guo1, Ping Li2

  • 1Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai, China.

Gene
|October 31, 2024
PubMed
Abstract

Insights

Tanshinones T1 and T2A show potential in treating lung cancer by upregulating let-7 and downregulating BORA. This study reveals a novel regulatory pathway involving MYCLo-5, offering new therapeutic insights for non-small cell lung cancer.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Oncology

Background:

  • Lung cancer remains a leading cause of cancer mortality globally.
  • Tanshinones, derived from Salvia miltiorrhiza, are being investigated for their therapeutic potential.
  • The specific mechanisms of tanshinone I (T1) and tanshinone IIA (T2A) in lung cancer require further elucidation.

Purpose of the Study:

  • To investigate the in vitro and in vivo effects of tanshinone T1 (T1) and tanshinone IIA (T2A) on non-small cell lung cancer (NSCLC).
  • To elucidate the molecular mechanisms underlying the anti-cancer activity of T1 and T2A, focusing on the let-7 microRNA family and its targets.
  • To identify novel regulatory pathways involving T1/T2A, let-7, BORA, and MYCLo-5 in NSCLC.

Main Methods:

  • In vivo xenograft tumor models were utilized to assess the efficacy of T1/T2A.
  • Next-generation sequencing (NGS) analyzed miRNA expression profiles in T1/T2A-treated A549 lung cancer cells.
  • Dual-luciferase reporter assays confirmed the interaction between let-7a-5p and its target gene, BORA.

Main Results:

  • T1/T2A treatment significantly upregulated the let-7 family and downregulated BORA in A549 cells.
  • BORA was identified as a direct downstream target of let-7.
  • Long non-coding RNA MYCLo-5 was upregulated by tanshinones; its knockdown promoted NSCLC cell cycle progression and proliferation.

Conclusions:

  • T1 and T2A demonstrate therapeutic effects on NSCLC both in vitro and in vivo.
  • A novel regulatory pathway (T1/T2A-let-7/BORA/MYCLo-5) was identified in NSCLC.
  • This pathway offers new therapeutic targets and insights for the treatment of lung cancer.
Keywords:
BORALet-7MYC/MYCLo-5NSCLCT1/T2A

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