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

Abstract

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.