Research Paper Advance Articles
PART1 facilitates tumorigenesis and inhibits ferroptosis by regulating the miR-490-3p/SLC7A11 axis in hepatocellular carcinoma
- 1 Department of Infectious Diseases, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China
- 2 Laboratory of Infection and Immunity, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China
- 3 Department of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China
Received: October 13, 2023 Accepted: June 10, 2024 Published: July 5, 2024
https://doi.org/10.18632/aging.206009How to Cite
Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Ferroptosis is associated with cancer progression and has a promising application for treating hepatocellular carcinoma (HCC). Long non-coding RNA (lncRNA) participates widely in the regulation of ferroptosis, but the key lncRNA regulators implicated in ferroptosis and their molecular mechanisms remain to be identified.
Methods: Bioinformatic analysis was performed in R based on The Cancer Genome Atlas Program (TCGA) public database. The relative expression of genes was detected by real-time quantitative PCR. Cell viability was assessed by the CCK8 assay. The cell cycle and apoptosis were detected by flow cytometry. Migration and invasion of HCC cells were detected by Transwell assay and wound healing assay. Expression of relevant proteins was detected by Western blotting. A dual-luciferase reporter assay was used to detect interactions between PART1 (or SLC7A11) and miR-490-3p.
Results: The PART1/miR-490-3p/SLC7A11 axis was identified as a potential regulatory pathway of ferroptosis in HCC. PART1 silencing reduced HCC cell proliferation, migration, and metastasis and promoted apoptosis and erastin-reduced ferroptosis. Further investigation revealed that PART1 acted as a competitive endogenous RNA (ceRNA) for miR-490-3p to enhance SLC7A11 expression. Overexpression of miR-490-3p downregulated the expression of SLC7A11, inhibiting the proliferation, invasion, and metastasis of HCC cells while promoting apoptosis and erastin-induced ferroptosis. Knockdown of PART1 in HCC cells significantly improved the sensitivity of HCC cells to sorafenib.
Conclusion: Our results revealed that the PART1/miR-490-3p/SLC7A11 axis enhances HCC cell malignancy and suppresses ferroptosis, which provides a new perspective for understanding of the function of long chain non-coding RNAs in HCC. The PART1/miR-490-3p/SLC7A11 axis may be target for improving sorafenib sensitivity in HCC.
Abbreviations
HCC: Hepatocellular Carcinoma; LncRNA: Long noncoding RNA; PART1: Prostate androgen-regulated transcript 1; SLC7A11: Solute Carrier Family 7 Member 11; GPX4: Glutathione peroxidase 4; ceRNA: Competitive endogenous RNA; DEGs: Differentially expressed genes; TCGA: The Cancer Genome Atlas Program; OS: overall survival; GSEA: Gene Set Enrichment Analysis; EMT: Epithelial-mesenchymal transition; DMEM: Dulbecco’s modified Eagle medium; FBS: Fetal bovine serum; PI: Propidium iodide; PBS: Phosphate buffered saline; OSCC: Oral squamous cell carcinoma.