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Int J Biol Sci 2022; 18(8):3156-3166. doi:10.7150/ijbs.68776 This issue Cite

Research Paper

LncRNA TNFRSF10A-AS1 promotes gastric cancer by directly binding to oncogenic MPZL1 and is associated with patient outcome

Donglei Sun1,2#, Hongyan Gou2,3#, Dandan Wang1, Chenyang Li1, Yan Li2, Hao Su2,3, Xiaohong Wang4, Xiaolan Zhang1✉, Jun Yu2,3✉

1. Department of Gastroenterology, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang 050000, Hebei, China.
2. Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
3. Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
4. Key laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China.
#Co-first authors.

✉ Corresponding authors: Professor Xiaolan Zhang, Department of Gastroenterology, The Second Hospital of Hebei Medical University, No. 80 Huanghe Road, Yuhua District, Shijiazhuang 050000, Hebei, China, E-mail: xiaolanzhcom; and Professor Jun Yu, More

Citation:
Sun D, Gou H, Wang D, Li C, Li Y, Su H, Wang X, Zhang X, Yu J. LncRNA TNFRSF10A-AS1 promotes gastric cancer by directly binding to oncogenic MPZL1 and is associated with patient outcome. Int J Biol Sci 2022; 18(8):3156-3166. doi:10.7150/ijbs.68776. https://www.ijbs.com/v18p3156.htm
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Abstract

Graphic abstract

Background: LncRNA is closely associated with the progression of human tumors. The role of lncRNA TNFRSF10A-AS1 (T-AS1) in gastric cancer (GC) is still unclear. We aim to investigate the functional significance and the underlying mechanisms of T-AS1 in the pathogenesis and progression of GC.

Experimental Design: The clinical impact of T-AS1 was assessed in 103 patients with GC. The biological function of T-AS1 was studied in vitro and in vivo. T-AS1 downstream effector were identified by RNA sequencing and RNA pulldown assay.

Results: T-AS1 was upregulated in GC cell lines and GC tissues as compared to adjacent non-cancer tissues (n = 47, P < 0.001). Multivariate analysis showed that GC patients with T-AS1 high expression had a significantly shortened survival (n=103, P < 0.05). T-AS1 significantly promoted GC cell proliferation, cell-cycle progression, and cell migration/invasion abilities, but suppressed cell apoptosis. Silencing of T-AS1 in GC cells exerted opposite effects in vitro. Knockout of T-AS1 significantly inhibited xenograft tumor growth in nude mice. Mechanistically, T-AS1 directly bound to Myelin Protein Zero Like 1 (MPZL1). MPZL1 showed an oncogenic function in GC by promoting cell proliferation, migration and invasion but inhibiting cell apoptosis. High expression of MPZL1 was associated with poor survivor of GC patients. Knockdown of MPZL1 could abrogate the effect of T-AS1 in the tumor-promoting function.

Conclusions: T-AS1 plays a pivotal oncogenic role in GC and is an independent prognostic factor for GC patients. The oncogenic function of T-AS1 is dependent on its direct downstream effector MPZL1.

Keywords: TNFRSF10A-AS1, Long non-coding RNA, Gastric cancer, MPZL1

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APA
Sun, D., Gou, H., Wang, D., Li, C., Li, Y., Su, H., Wang, X., Zhang, X., Yu, J. (2022). LncRNA TNFRSF10A-AS1 promotes gastric cancer by directly binding to oncogenic MPZL1 and is associated with patient outcome. International Journal of Biological Sciences, 18(8), 3156-3166. https://doi.org/10.7150/ijbs.68776.

ACS
Sun, D.; Gou, H.; Wang, D.; Li, C.; Li, Y.; Su, H.; Wang, X.; Zhang, X.; Yu, J. LncRNA TNFRSF10A-AS1 promotes gastric cancer by directly binding to oncogenic MPZL1 and is associated with patient outcome. Int. J. Biol. Sci. 2022, 18 (8), 3156-3166. DOI: 10.7150/ijbs.68776.

NLM
Sun D, Gou H, Wang D, Li C, Li Y, Su H, Wang X, Zhang X, Yu J. LncRNA TNFRSF10A-AS1 promotes gastric cancer by directly binding to oncogenic MPZL1 and is associated with patient outcome. Int J Biol Sci 2022; 18(8):3156-3166. doi:10.7150/ijbs.68776. https://www.ijbs.com/v18p3156.htm

CSE
Sun D, Gou H, Wang D, Li C, Li Y, Su H, Wang X, Zhang X, Yu J. 2022. LncRNA TNFRSF10A-AS1 promotes gastric cancer by directly binding to oncogenic MPZL1 and is associated with patient outcome. Int J Biol Sci. 18(8):3156-3166.

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