MiR-4732-3p Prevents Lung Cancer Progression via Inhibition of the TBX15/TNFSF11 Axis

Abstract

Aim: Possible roles of miRNAs in cancer treatment have been highly studied. This study aimed to elucidate the role of miR-4732-3p in lung cancer. Methods: Bioinformatics analysis was conducted to predict miR-4732-3p-related mRNA targets in lung cancer. Following interaction determination between miR-4732-3p and TBX15 as well as between TBX15 and TNFSF11, their in vitro and in vivo roles were assayed. Results: miR-4732-3p negatively targeted TBX15, which upregulated TNFSF11 by enhancing the activity of the TNFSF11 promoter. Overexpression of miR-4732-3p or silencing of TBX15 or TNFSF11 inhibited the malignant phenotype of lung cancer cells and reduced tumorigenicity in vivo. Conclusion: Overall, this study highlighted the inhibitory role of miR-4732-3p in lung cancer progression through the TBX15/TNFSF11 axis.

Plain language summary

This study describes the role of miR-4732-3p in lung cancer. The authors conducted bioinformatics analysis to predict miR-4732-3p-related mRNA targets in lung cancer. Then they analyzed the potential interaction between miR-4732-3p and TBX15 and between TBX15 and TNFSF11. To evaluate their effects on the progression of lung cancer, the authors performed in vitro and in vivo assays. They discovered that miR-4732-3p negatively targeted TBX15, which upregulated TNFSF11 by enhancing the activity of TNFSF11 promoter. Overexpression of miR-4732-3p or silencing of TBX15 or TNFSF11 inhibited the malignant phenotype of lung cancer cells and reduced tumorigenicity in vivo. This study, which has identified potential for the miR-4732-3p/TBX15/TNFSF11 axis as an antioncogenic tool, opens the possibility for better monitoring of lung cancer.

Tweetable abstract

This study, which has identified potential for the miR-4732-3p/TBX15/TNFSF11 axis as an antioncogenic tool, opens the possibility for better monitoring of lung cancer.

Keywords::

• invasion
• lung cancer
• migration
• miR-4732-3p
• proliferation
• promoter activity
• TBX15
• TNFSF11

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2023-0009

PF Li and L Zhao designed the study. Y Li, SP Bai and Y Zhang collated the data, carried out data analyses and produced the initial draft of the manuscript. PF Li and L Zhao contributed to drafting the manuscript. All authors have read and approved the final submitted manuscript.

Financial & competing interests disclosure

This study was supported by Wu Jieping Medical Foundation. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The current study was granted by the Ethics Committee of Harbin Medical University Cancer Hospital and performed in strict accordance with the Declaration of Helsinki. All participants signed informed consent documentation before sample collection. Animal experiments were ratified by the Animal Ethics Committee of Harbin Medical University Cancer Hospital and strictly carried out in line with the Guide for the Care and Use of Laboratory Animals published by the US NIH.

Data availability statement

The data underlying this article will be shared on reasonable request to the corresponding author.

Additional information

Funding

This study was supported by Wu Jieping Medical Foundation. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.