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LncRNA HOXC-AS3 Accelerates Malignant Proliferation of Cervical Cancer Cells Via Stabilizing KDM5B

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Specialty Oncology
Date 2024 Jun 6
PMID 38842683
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Abstract

Background: Cervical cancer (CC) is a common malignancy amongst women globally. Ubiquitination plays a dual role in the occurrence and development of cancers. This study analyzed the mechanism of long noncoding RNA HOXC cluster antisense RNA 3 (lncRNA HOXC-AS3) in malignant proliferation of CC cells via mediating ubiquitination of lysine demethylase 5B (KDM5B/JARID1B).

Methods: The expression patterns of lncRNA HOXC-AS3 and KDM5B were measured by real-time quantitative polymerase chain reaction or Western blot analysis. After transfection with lncRNA HOXC-AS3 siRNA and pcDNA3.1-KDM5B, proliferation of CC cells was assessed by the cell counting kit-8, colony formation, and 5-Ethynyl-2'-deoxyuridine staining assays. The xenograft tumor model was established to confirm the impact of lncRNA HOXC-AS3 on CC cell proliferation in vivo by measuring tumor size and weight and the immunohistochemistry assay. The subcellular location of lncRNA HOXC-AS3 and the binding of lncRNA HOXC-AS3 to KDM5B were analyzed. After treatment of lncRNA HOXC-AS3 siRNA or MG132, the protein and ubiquitination levels of KDM5B were determined. Thereafter, the interaction and the subcellular co-location of tripartite motif-containing 37 (TRIM37) and KDM5B were analyzed by the co-immunoprecipitation and immunofluorescence assays.

Results: LncRNA HOXC-AS3 and KDM5B were upregulated in CC tissues and cells. Depletion of lncRNA HOXC-AS3 repressed CC cell proliferation and in vivo tumor growth. Mechanically, lncRNA HOXC-AS3 located in the nucleus directly bound to KDM5B, inhibited TRIM37-mediated ubiquitination of KDM5B, and upregulated the protein levels of KDM5B. KDM5B overexpression attenuated the inhibitory role of silencing lncRNA HOXC-AS3 in CC cell proliferation in vivo and in vitro.

Conclusion: Nucleus-located lncRNA HOXC-AS3 facilitated malignant proliferation of CC cells via stabilization of KDM5B protein levels.

References
1.
Li Y, Xie P, Lu L, Wang J, Diao L, Liu Z . An integrated bioinformatics platform for investigating the human E3 ubiquitin ligase-substrate interaction network. Nat Commun. 2017; 8(1):347. PMC: 5570908. DOI: 10.1038/s41467-017-00299-9. View

2.
Zhang Z, Zhang H, Sun H, Liu H, Liu M, Zhou Z . KDM5B promotes breast cancer cell proliferation and migration via AMPK-mediated lipid metabolism reprogramming. Exp Cell Res. 2019; 379(2):182-190. DOI: 10.1016/j.yexcr.2019.04.006. View

3.
Zhao R, Song J, Jin Y, Liu Y . Long noncoding RNA HOXC-AS3 enhances the progression of cervical cancer via activating ErbB signaling pathway. J Mol Histol. 2021; 52(5):991-1006. DOI: 10.1007/s10735-021-10007-z. View

4.
Gong J, Yan S, Yu H, Zhang W, Zhang D . Increased Expression of Lysine-Specific Demethylase 5B (KDM5B) Promotes Tumor Cell Growth in Hep3B Cells and is an Independent Prognostic Factor in Patients with Hepatocellular Carcinoma. Med Sci Monit. 2018; 24:7586-7594. PMC: 6210936. DOI: 10.12659/MSM.910844. View

5.
Bueno M, Richard S . SUMOylation negatively modulates target gene occupancy of the KDM5B, a histone lysine demethylase. Epigenetics. 2013; 8(11):1162-75. DOI: 10.4161/epi.26112. View