MiR-421 Promotes Lipid Metabolism by Targeting PTEN Via Activating PI3K/AKT/mTOR Pathway in Non-Small Cell Lung Cancer

Abstract

Aims: We aim to investigate the effects of miR-421 on lipid metabolism in non-small cell lung cancer (NSCLC). Methods: The miR-421 expression and PTEN mRNA level in tumor tissues, adjacent normal tissues, human lung epithelial cells and NSCLC cell lines were detected with reverse transcription quantitative real-time PCR. Results: MiR-421 was increased, and PTEN was reduced remarkably in tumor tissues and NSCLC cell lines. Down-regulated miR-421 suppressed lipid accumulation, cell proliferation, migration and invasion, whereas overexpression of miR-421 had the opposite effects. MiR-421 directly targeted PTEN and negatively regulated PTEN expression. MiR-421 activated PI3K/AKT/mTOR pathway through regulating PTEN. Conclusion: MiR-421 promotes lipid metabolism through targeting PTEN via PI3K/AKT/mTOR pathway activation in NSCLC, indicating that miR-421 can be a latent therapeutic target for NSCLC.

Lay abstract

Numerous miRNAs are dysregulated in lung cancer, which play vital roles in tumor progression. Currently, the alteration of lipid metabolism has been recognized as a critical hallmark of cancer. In the present study, we found that miR-421 targeted PTEN to promote lipid metabolism via activation of PI3K/AKT/mTOR signaling pathway in NSCLC. This study might provide a deeper insight into the prognostics strategies for lung cancer by understanding the specific mechanism of miR-421 in lipid metabolism.

Graphical abstract

Keywords::

• lipid metabolism
• miR-421
• non-small cell lung cancer
• PI3K/AKT/mTOR pathway
• PTEN

YJ Xu: conceptualization and data curation; RS Wei: software, visualization, writing and original draft preparation; XH Li: methodology, writing – reviewing and editing; Q Li: investigation, writing and original draft preparation; XF Zhuang: methodology, visualization and validation; J Rong Yu: data curation and supervision.

Acknowledgments

The authors sincerely acknowledge all the members of their laboratory for their contributions.

Financial & competing interests disclosure

This project was funded by the Shanxi Science and Technology Department, Applied Basic Research Projects of Shanxi Province (no. 201801D121309) and Key Research and Development (R&D) Projects of Shanxi Province (no. 201903D321168). The authors have no other 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 apart from those disclosed.

Funded writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All human studies were approved by Changzhou Cancer Hospital Affiliated to Soochow University the Ethics Committee of the Chinese Academy of Medical Science, animal studies were approved by The Second Affiliated Hospital of Shanxi Medical University. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Data sharing statement

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This project was funded by the Shanxi Science and Technology Department, Applied Basic Research Projects of Shanxi Province (no. 201801D121309) and Key Research and Development (R&D) Projects of Shanxi Province (no. 201903D321168). The authors have no other 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 apart from those disclosed. Funded writing assistance was utilized in the production of this manuscript.