The m6A-induced lncRNA CASC8 promotes proliferation and chemoresistance via upregulation of hnRNPL in esophageal squamous cell carcinoma

Wu, Qingnan; Zhang, Hongyue; Yang, Di; Min, Qingjie; Wang, Yan; Zhang, Weimin; Zhan, Qimin

doi:10.7150/ijbs.71234

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Int J Biol Sci 2022; 18(13):4824-4836. doi:10.7150/ijbs.71234 This issue Cite

Research Paper

The m6A-induced lncRNA CASC8 promotes proliferation and chemoresistance via upregulation of hnRNPL in esophageal squamous cell carcinoma

Qingnan Wu^1,3*, Hongyue Zhang^1*, Di Yang^1*, Qingjie Min¹, Yan Wang¹, Weimin Zhang^1,2,3, Qimin Zhan^1,2,3✉

1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
2. Shenzhen Bay Laboratory, Shenzhen 518132, China
3. Research Unit of Molecular Cancer Research, Chinese Academy of Medical Sciences, Beijing 100021, China
*Those authors contributed equally to the work

Citation:

Wu Q, Zhang H, Yang D, Min Q, Wang Y, Zhang W, Zhan Q. The m6A-induced lncRNA CASC8 promotes proliferation and chemoresistance via upregulation of hnRNPL in esophageal squamous cell carcinoma. Int J Biol Sci 2022; 18(13):4824-4836. doi:10.7150/ijbs.71234. https://www.ijbs.com/v18p4824.htm

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Abstract

Long noncoding RNAs (lncRNAs) are dysregulated in many cancers. Here, we identified the molecular mechanisms of lncRNA Cancer Susceptibility Candidate 8 (CASC8) in promoting the malignancy of esophageal squamous cell carcinoma (ESCC). CASC8 was highly overexpressed in ESCC tissues and upregulation of CASC8 predicted poor prognosis in ESCC patients. Moreover, CASC8 decreased the cisplatin sensitivity of ESCC cells and promoted ESCC tumor growth in vivo. Mechanistically, CASC8 interacted with heterogeneous nuclear ribonucleoprotein L (hnRNPL) and inhibited its polyubiquitination and proteasomal degradation, thus stabilizing hnRNPL protein levels and activating the Bcl2/caspase3 pathway. Additionally, AlkB Homolog 5, RNA demethylase (ALKBH5)-mediated m6A demethylation stabilized the CASC8 transcript, resulting in CASC8 upregulation. Taken together, these findings identified an oncogenic function of CASC8 in the progression of ESCC, which suggest that CASC8 might become a potential prognostic biomarker in ESCC.

Keywords: lncRNA, esophageal squamous cell carcinoma, cell apoptosis, m6A demethylation, CASC8

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APA

Wu, Q., Zhang, H., Yang, D., Min, Q., Wang, Y., Zhang, W., Zhan, Q. (2022). The m6A-induced lncRNA CASC8 promotes proliferation and chemoresistance via upregulation of hnRNPL in esophageal squamous cell carcinoma. International Journal of Biological Sciences, 18(13), 4824-4836. https://doi.org/10.7150/ijbs.71234.

ACS

Wu, Q.; Zhang, H.; Yang, D.; Min, Q.; Wang, Y.; Zhang, W.; Zhan, Q. The m6A-induced lncRNA CASC8 promotes proliferation and chemoresistance via upregulation of hnRNPL in esophageal squamous cell carcinoma. Int. J. Biol. Sci. 2022, 18 (13), 4824-4836. DOI: 10.7150/ijbs.71234.

NLM

CSE

Wu Q, Zhang H, Yang D, Min Q, Wang Y, Zhang W, Zhan Q. 2022. The m6A-induced lncRNA CASC8 promotes proliferation and chemoresistance via upregulation of hnRNPL in esophageal squamous cell carcinoma. Int J Biol Sci. 18(13):4824-4836.

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