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Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:

2024 15

Page:

2703-2715

Research Field:

Publishing date:

Info

Title:

Circular RNA hsa_circ_0078767 regulates ferroptosis in lung cancer cells through miR-330-3p/p53 axis

Author(s):

WANG Yinghui¹; JIANG Hua²; LU Lin³; YE Lijuan⁴; HOU Fei¹; PENG Xiaoqi¹; CAI Haolin¹; ZHENG Xihua¹; CHEN Ting¹

Keywords:

hsa_circ_0078767; miR-330-3p; TP53; lung cancer; ferroptosis

PACS:

R734.2

DOI:

10.3969/j.issn.1672-4992.2024.15.004

Abstract:

Objective:To investigate the effect of Circular RNAs (hsa_circ_0078767) on ferroptosis in lung cancer cells by modulating miR-330-3p/p53 signaling pathway.Methods:Expression of hsa_circ_0078767 was detected by qRT-PCR in four human lung cancer cell lines (HCC827,A-549,Calu-3,and H1975) and one normal lung epithelial cell line,BEAS-2B.An overexpression vector (oe-circ) of hsa_circ_0078767 was transfected in A-549 and H1975 cells.RNA FISH was used to determine the cytoplasmic localization of hsa_circ_0078767.CCK-8,colony formation,EdU staining,FACS analysis,and flow cytometry were used to detect activity,proliferation,apoptosis,and ROS in A-549 and H1975 cells,respectively.Iron assay kit was used to detect cellular iron content,and Western blot detected the expression of miR-330-3p,cleaved Caspase3 and cleaved PARP in cells.RNA pull-down assay was used to analyze the binding efficiency of hsa_circ_0078767 and miR-330-3p binding site.RNA-binding protein immunoprecipitation (RIP) assay detected the mRNA level of hsa_circ_0078767 and miR-330-3p.Dual luciferase reporter gene assay detected the targeting relationship between hsa_circ_0078767 and miR-330-3p,and subcutaneous injection of A-549-vector and A549-oe-circ cells (1×106) into the abdomen of six-week-old male nude mice was used to establish a living xenograft animal model.Results:We found low expression of hsa_circ_0078767 in lung cancer cells and the regulatory function of hsa_circ_0078767 on ferroptosis during malignant progression of lung cancer.Elevated levels of iron,Fe2+ and ROS were found in lung cancer cells overexpressing hsa_circ_0078767.The ferroptosis inducer erastin decreased cell viability,while overexpression of hsa_circ_0078767 enhanced the inhibitory effect of erastin on lung cancer cells.Mechanistically,hsa_circ_0078767 could affect the expression of p53 through sponge adsorption of miR-330-3p.Up-regulation of miR-330-3p and knockdown of p53 reversed the effects of hsa_circ_0078767 overexpression on lung cancer cells.Conclusion:hsa_circ_0078767 may promote ferroptosis in lung cancer cells through the miR-330-3p/p53 axis thereby inhibiting lung cancer progression.

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Memo

Memo:

National Natural Science Foundation of China（No.81960426）;国家自然科学基金地区科学基金项目（编号：81960426）

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Last Update: 2024-06-28