Long non-coding RNA ESCCAL-1 promotes esophageal squamous cell carcinoma by down regulating the negative regulator of APOBEC3G

被引:22
|
作者
Liu, Jia [1 ]
Mayekar, Manasi K. [2 ]
Wu, Wei [2 ]
Yan, Ming [3 ]
Guan, Hongya [1 ]
Wang, Jinwu [4 ]
Zaman, Aubhishek [2 ]
Cui, Yuanbo [1 ]
Bivona, Trever G. [2 ]
Choudhry, Hani [5 ]
Xing, Qinghe [6 ,7 ]
Cao, Wei [1 ]
机构
[1] Zhengzhou Univ, Translat Med Ctr, Zhengzhou Cent Hosp, 16 Tongbai North Rd, Zhengzhou 450007, Peoples R China
[2] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
[3] Zhengzhou Univ, Basic Med Coll, Zhengzhou, Peoples R China
[4] Linzhou Canc Hosp, Dept Pathol, Linzhou, Peoples R China
[5] King Abdulaziz Univ, Fac Sci, King Fahd Med Res Ctr, Dept Biochem,Canc & Mutagenesis Unit, Jeddah, Saudi Arabia
[6] Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China
[7] Fudan Univ, Childrens Hosp, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
LncRNA; Esophageal squamous cell carcinoma; miR-590-3p; PI3K-Akt pathway; SIGNALING PATHWAY; POOR-PROGNOSIS; CANCER; APOPTOSIS; MIGRATION; INVASION; GENE; PROLIFERATION; CONTRIBUTES; SUPPRESSES;
D O I
10.1016/j.canlet.2020.09.001
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The expression of lncRNA ESCCAL-1 is upregulated in esophageal squamous cell carcinoma (ESCC). However, the molecular pathways regulated by ESCCAL-1 in esophageal cancer remain obscure. We found that high expression of the lncRNA ESCCAL-1 in human ESCC tumors correlated with worse clinicopathologic features. Furthermore, depletion of ESCCAL-1 in ESCC models inhibited the cellular processes associated with malignancy, including proliferation, migration and invasion, resistance to apoptosis, and impaired tumor growth in mice. Using a combinatorial approach, we discovered that ESCCAL-1 regulates malignant phenotypes in ESCC by acting as a molecular sponge for miR-590-3p. This interaction prevents miR-590-3p from suppressing APOBEC3G expression. Increased APOBEC3G was also a biomarker of worse clinicopathologic features in human ESCC tumors. Depletion of ESSCAL-1 or APOBEC3G, or overexpression of miR-590-3p resulted in increased apoptosis due to downregulation of the PI3K/Akt signaling. This study demonstrates that the lncRNA ESCCAL-1 promotes malignant features of ESCC by relieving the inhibitory effect of miR-590-3p on APOBEC3G expression and identifies potential biomarkers or therapeutic targets to improve ESCC treatment outcomes.
引用
收藏
页码:217 / 227
页数:11
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