J Cancer 2021; 12(4):1073-1084. doi:10.7150/jca.51292 This issue

Research Paper

Long Noncoding RNA FAM225A Promotes Esophageal Squamous Cell Carcinoma Development and Progression via Sponging MicroRNA-197-5p and Upregulating NONO

Pengyuan Zhu1, Haitao Huang2, Shaorui Gu2, Zhenchuan Liu2, Xin Zhang2, Kaiqin Wu2, Tiancheng Lu2, Lei Li2, Chenglai Dong2, Chongjun Zhong1✉, Yongxin Zhou2✉

1. Department of thoracic and Cardiovascular Surgery, the Second Affiliated Hospital of Nantong University, School of Medicine, Nantong University, Nantong, 226001, China.
2. Department of thoracic and Cardiovascular Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.

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Citation:
Zhu P, Huang H, Gu S, Liu Z, Zhang X, Wu K, Lu T, Li L, Dong C, Zhong C, Zhou Y. Long Noncoding RNA FAM225A Promotes Esophageal Squamous Cell Carcinoma Development and Progression via Sponging MicroRNA-197-5p and Upregulating NONO. J Cancer 2021; 12(4):1073-1084. doi:10.7150/jca.51292. Available from https://www.jcancer.org/v12p1073.htm

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Abstract

Esophageal squamous cell carcinoma (ESCC) is the major subclass of esophageal cancer and one of the most life-threatening malignancies with high morbidity and mortality. Long noncoding RNAs (lncRNAs) participate in tumorigenesis and metastasis of various tumors. Here, we investigated the function of a newly identified lncRNA FAM225A in ESCC. LncRNA FAM225A expression was significantly higher in ESCC and predicted poor prognosis of ESCC patients. We confirmed that upregulation of FAM225A in ESCC and overexpression of FAM225A was associated with poor outcome in ESCC patients using TCGA ESCC cohort. Knockdown of FAM225A significantly inhibited cell growth, migration and invasion of ESCC cells in vitro and inhibited ESCC xenograft development in vivo. Mechanistically, we demonstrated that lncRNA FAM225A functioned as a competing endogenous RNA (ceRNA) via sponging miR-197-5p. LncRNA FAM225A exerted its regulatory function on ESCC proliferation and metastasis via modulating expression of miR-197-5p. MiR-197-5p overexpression antagonized the function of FAM225A, with decreased cell growth and invasion. Moreover, we identified that RNA binding protein NONO was a direct target of miR-197-5p and miR-197-5p negatively regulated NONO expression and TGF-β signaling in ESCC cells. In summary, our findings suggest that lncRNA FAM225A promotes ESCC development and progression via sponging miR-197-5p and upregulating NONO expression. These results suggest that lncRNA FAM225A could be explored as a new therapy target in ESCC treatment.

Keywords: FAM225A, microRNA-197-5p, NONO, ESCC