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

Autor: Li Y; Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai, China., Guo Z; Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai, China., Li P; School of Life Sciences, Shanghai University, Shanghai, China., Guo J; Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai, China., Wang H; Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai, China., Pan W; Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai, China., Wu F; Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai, China., Li J; School of Pharmaceutical Engineering, Zhejiang Pharmaceutical College, Ningbo, China. Electronic address: pingljj@126.com., Zhou J; Nutrition/Metabolism Laboratory, Beth Israel Deaconess Medical Center Harvard Medical School, USA. Electronic address: jrzhou@bidmc.harvard.edu., Ma Z; Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, Shanghai, China. Electronic address: zlma@shu.edu.cn.
Jazyk: angličtina
Zdroj: Gene [Gene] 2025 Jan 30; Vol. 935, pp. 149058. Date of Electronic Publication: 2024 Oct 29.
DOI: 10.1016/j.gene.2024.149058
Abstrakt: Background: Lung cancer is the leading cause of cancer-related deaths worldwide. Tanshinones are a group of compounds in Salvia miltiorrhiza. Although the effects of tanshinone I (T1) and tanshinone IIA (T2A) are widely concerned, the mechanisms of T1 and T2A in lung cancer is rarely studied.
Experimental Procedure: Xenograft tumor growth was performed to detect the role of T1/T2A in vivo. Next-generation sequencing of miRNA expression profiles in T1/T2A-treated A549 cells showed that T1/T2A upregulated the expression of the let-7 family. Then, let-7a-5p and its downstream target gene BORA were identified as the research objects in this paper. Mechanistically, we examined the interplay between miR-let-7 and BORA through the dual-luciferase reporter assay. Finally, the potential regulatory role of T1/T2A on Lin28B and MYC was explored.
Results: This study found that the let-7 family was significantly up-regulated via "Next-generation" sequencing (NGS) in the T1/T2A-treated A549 cell line, while BORA was downregulated. BORA was confirmed as a direct target of let-7. LncRNA MYCLo-5 was up-regulated after treatment with tanshinones. Knockdown of MYCLo-5 promoted the cell cycle and proliferation of non-small cell lung cancer (NSCLC) cells.
Conclusions: This study explored the effects of tanshinone T1 and T2A on NSCLC in vitro and in vivo, revealing the T1/T2A-let-7/BORA/MYCLo-5 regulatory pathway, which provided new insights for lung cancer treatment.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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