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Identification of a Novel circ_0010235/miR-1249-3p/HOXA13 Axis in Lung Adenocarcinoma

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Abstract

Lung adenocarcinoma (LUAD) is an aggressive malignancy with a poor prognosis. In this study, we explored the critical role and mechanism of circ_0010235 in the pathogenesis of LUAD. The expression levels of circ_0010235, microRNA (miR)-1249-3p, and homeobox A13 (HOXA13) were gauged by quantitative real-time PCR (qRT-PCR) and Western blot. Cell proliferation, cycle progression, migration, and invasion were evaluated by Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2′-Deoxyuridine (Edu), flow cytometry, and transwell assays, respectively. The direct relationship between miR-1249-3p and circ_0010235 or HOXA13 was validated by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. Xenograft experiments were used to examine the role of circ_0010235 in vivo. Circ_0010235 was significantly overexpressed in human LUAD. Silencing of circ_0010235 hindered LUAD cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) in vitro, as well as diminished tumor growth in vivo. Mechanistically, circ_0010235 targeted and inhibited miR-1249-3p. Moreover, circ_0010235 depletion repressed cell malignant behaviors by upregulating miR-1249-3p. HOXA13 was identified as a direct and functional target of miR-1249-3p. Furthermore, circ_0010235 regulated HOXA13 expression by competing for shared miR-1249-3p. Our findings demonstrate that the circ_0010235/miR-1249-3p/HOXA13 axis is implicated in the pathogenesis of LUAD.

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Authors and Affiliations

  1. Department of Thoracic Surgery, Shanxi Provincial Cancer Hospital, No.3 Worker’s New Street, Xinhualing District, Taiyuan, 030001, Shanxi Province, China

    Jiancheng Liu & Zejun Fu

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  1. Jiancheng Liu
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  2. Zejun Fu
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Contributions

JL was responsible for drafting the manuscript. JL and ZF contributed to the analysis and interpretation of the data. JL and ZF contributed in the data collection. All authors read and approved the final manuscript.

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Correspondence to Zejun Fu.

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The authors declare that they have no financial conflict of interest.

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Written informed consent was obtained from patients with approval by the Institutional Review Board in Shanxi Provincial Cancer Hospital.

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Supplementary Information

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Supplementary file1 (DOCX 60 KB) Supplement Table 1 Sequences of qRT-PCR primers

10528_2021_10181_MOESM2_ESM.tif

Supplementary file2 (TIF 354 KB) Supplement Figure 1 Correlation between the expression of circ_0010235, miR-1249-3p or HOXA13 and the overall survival of patients. All patients were divided into two groups according to the median of circ_0010235, miR-1249-3p or HOXA13 expression. A Correlation between circ_0010235 expression and patient overall survival. B Correlation between miR-1249-3p expression and patient overall survival. C Correlation between HOXA13 expression and patient overall survival

10528_2021_10181_MOESM3_ESM.tif

Supplementary file3 (TIF 2991 KB) Supplement Figure 2 Selection of HOXA13 in this study. A Venn diagram showing the putative targets of miR-1249-3p predicted by both Starbase3.0 and TargetScan7.2. B–I Correlation between the expression of eight genes and patient survival analyzed by the Starbase3.0 database. J qRT-PCR of four genes in LUAD tissues and matched nontumor tissues from the same patients (n = 3). *P < 0.05

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Liu, J., Fu, Z. Identification of a Novel circ_0010235/miR-1249-3p/HOXA13 Axis in Lung Adenocarcinoma. Biochem Genet 60, 1657–1675 (2022). https://doi.org/10.1007/s10528-021-10181-5

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