2. Academic Validation
  3. LncRNA HOXC-AS3 accelerates malignant proliferation of cervical cancer cells via stabilizing KDM5B

LncRNA HOXC-AS3 accelerates malignant proliferation of cervical cancer cells via stabilizing KDM5B

  • J Cancer Res Clin Oncol. 2024 Jun 6;150(6):294. doi: 10.1007/s00432-024-05799-y.
Jie Li # 1,  Fang Hou # 1,  Zhenghua Teng 1,  Weiwei Xia 1,  Jie Peng 2
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Suzhou Wuzhong People's Hospital, Jiangsu Province, No. 61, Dongwu North Road, Suzhou City, 215128, China.
  • 2 Department of Obstetrics and Gynecology, Suzhou Wuzhong People's Hospital, Jiangsu Province, No. 61, Dongwu North Road, Suzhou City, 215128, China. pengjie_08@163.com.
  • # Contributed equally.
PMID: 38842683 DOI: 10.1007/s00432-024-05799-y
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.

Keywords

Cervical cancer; KDM5B; LncRNA HOXC-AS3; Proliferation; TRIM37.

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