Abstract
Long noncoding RNAs (lncRNAs) play important roles in modulating the tumorigenesis and progression of malignant tumors. LINC02086 is a newly identified oncogene associated with tumorigenesis, but its role in pancreatic cancer (PC) has not been fully elucidated. In this study we examined the expression levels of LINC02086, miR-342-3p, and CA9 in PC. The relationship of ferroptosis with these factors was analyzed by detecting the expression levels of Fe2+, reactive oxygen species (ROS), and ferroptosis marker proteins. The expression of these genes was altered to observe their effects on cell proliferation, migration, and invasion ability. Bioinformatics was used to predict target genes, and the binding relationship was verified luciferase reporter assay. Finally, the function of LINC02086 was evaluated in vivo. The findings suggest that LINC02086 is highly expressed in PC tissues and cell lines and is correlated with a poor prognosis. In vitro experiments demonstrated that LINC02086 knockdown promoted ferroptosis in PC cells to suppress their malignant phenotype. LINC02086 acts as a competitive endogenous RNA that adsorbed miR-342-3p. miR-342-3p hinders the malignant progression of PC by promoting ferroptosis. In addition, miR-342-3p targets CA9 and affects its function. Further mechanistic studies revealed that LINC02086 inhibits ferroptosis and promotes PC progression by acting as a sponge for miR-342-3p to upregulate CA9 expression. In vivo experiments further confirmed this mechanism. Taken together, LINC02086 upregulates CA9 expression by competitively binding with miR-342-3p, thereby inhibiting ferroptosis in PC cells and promoting their malignant phenotype. The results of our study provide new insights into how LINC02086 contributes to the progression of PC.
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The current study was supported by the National Natural Science Foundation of China (81860418), the Natural Science Foundation of Jiangxi Province (20202ACB206007).
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Xiong YP and Xiao WD designed the project and wrote the manuscript. Xiong YP, Kong XY, Tu SJ and Xin WP carried out the experiments. Wei YY, Yi SQ and Wan RH conducted bioinformatic and data analysis. Xiong YP and Xiao WD reviewed the manuscript and provided ideas for the study. All authors read and approved the final manuscript.
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and consent participate The study involving human participants was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital of Nanchang University (2022-4-027). All patients signed written informed consent and all experimental protocols were implemented in accordance with relevant regulations. The animal experiments were approved by the animal Ethics Committee of the First Affiliated Hospital of Nanchang University (2022-4-027).
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Supplementary Table S1. List of predicted binding genes.
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Xiong, Y., Kong, X., Tu, S. et al. LINC02086 inhibits ferroptosis and promotes malignant phenotypes of pancreatic cancer via miR-342-3p/CA9 axis. Funct Integr Genomics 24, 49 (2024). https://doi.org/10.1007/s10142-024-01329-8
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DOI: https://doi.org/10.1007/s10142-024-01329-8