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ZNF674-AS1 antagonizes miR-423-3p to induce G0/G1 cell cycle arrest in non-small cell lung cancer cells
Cellular & Molecular Biology Letters ( IF 9.2 ) Pub Date : 2021-02-22 , DOI: 10.1186/s11658-021-00247-y
Yu Liu 1 , Risheng Huang 2 , Deyao Xie 1 , Xiaoming Lin 1 , Liangcheng Zheng 1
Affiliation  

ZNF674-AS1, a recently characterized long noncoding RNA, shows prognostic significance in hepatocellular carcinoma and glioma. However, the expression and function of ZNF674-AS1 in non-small cell lung cancer (NSCLC) are unclear. In this work, we investigated the expression of ZNF674-AS1 in 83 pairs of NSCLC specimens and adjacent noncancerous lung tissues. The clinical significance of ZNF674-AS1 in NSCLC was analyzed. The role of ZNF674-AS1 in NSCLC growth and cell cycle progression was explored. Our data show that ZNF674-AS1 expression is decreased in NSCLC compared to normal tissues. ZNF674-AS1 downregulation is significantly correlated with advanced TNM stage and decreased overall survival of NSCLC patients. Overexpression of ZNF674-AS1 inhibits NSCLC cell proliferation, colony formation, and tumorigenesis, which is accompanied by a G0/G1 cell cycle arrest. Conversely, knockdown of ZNF674-AS1 enhances the proliferation and colony formation of NSCLC cells. Biochemically, ZNF674-AS1 overexpression increases the expression of p21 through downregulation of miR-423-3p. Knockdown of p21 or overexpression of miR-423-3p blocks ZNF674-AS1-mediated growth suppression and G0/G1 cell cycle arrest. In addition, ZNF674-AS1 expression is negatively correlated with miR-423-3p in NSCLC specimens. ZNF674-AS1 suppresses NSCLC growth by downregulating miR-423-3p and inducing p21. This work suggests the therapeutic potential of ZNF674-AS1 in the treatment of NSCLC.

中文翻译:


ZNF674-AS1拮抗miR-423-3p诱导非小细胞肺癌细胞G0/G1细胞周期停滞



ZNF674-AS1 是一种最近鉴定的长非编码 RNA,在肝细胞癌和神经胶质瘤中显示出预后意义。然而,ZNF674-AS1在非小细胞肺癌(NSCLC)中的表达和功能尚不清楚。在这项工作中,我们研究了 ZNF674-AS1 在 83 对 NSCLC 标本和邻近非癌性肺组织中的表达。分析ZNF674-AS1在NSCLC中的临床意义。探讨了 ZNF674-AS1 在 NSCLC 生长和细胞周期进展中的作用。我们的数据显示,与正常组织相比,NSCLC 中 ZNF674-AS1 的表达降低。 ZNF674-AS1 下调与 NSCLC 患者的晚期 TNM 分期和总生存率降低显着相关。 ZNF674-AS1 的过表达可抑制 NSCLC 细胞增殖、集落形成和肿瘤发生,并伴有 G0/G1 细胞周期停滞。相反,ZNF674-AS1 的敲低会增强 NSCLC 细胞的增殖和集落形成。从生化角度来看,ZNF674-AS1 过表达通过下调 miR-423-3p 增加 p21 的表达。 p21 的敲低或 miR-423-3p 的过表达可阻断 ZNF674-AS1 介导的生长抑制和 G0/G1 细胞周期停滞。此外,NSCLC标本中ZNF674-AS1的表达与miR-423-3p呈负相关。 ZNF674-AS1 通过下调 miR-423-3p 和诱导 p21 抑制 NSCLC 生长。这项工作表明 ZNF674-AS1 在治疗 NSCLC 中的治疗潜力。
更新日期:2021-02-22
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