%A Li, Decheng 
%A Wan, Meiling 
%A Liu, Xiaoling 
%A Ojha, Suvash Chandra 
%A Sheng, Yunjian 
%A Li, Yaling 
%A Sun, Changfeng 
%A Deng, Cunliang 
%D 2024
%T PART1 facilitates tumorigenesis and inhibits ferroptosis by regulating the miR-490-3p/SLC7A11 axis in hepatocellular carcinoma
%! PART1 facilitates tumorigenesis and inhibits ferroptosis by regulating the miR-490-3p/SLC7A11 axis in hepatocellular carcinoma
%K hepatocellular carcinoma, ferroptosis, PART1, miR-490-3p, SLC7A11
%X 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.
%U https://doi.org/10.18632/aging.206009
%J Aging
%0 Journal Article
%V 16
%N 14
%P 11339-11358
%R 10.18632/aging.206009
%@ 1945-4589