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长链非编码 RNA PITPNA-AS1 通过靶向 miR-876-5p/c-MET 轴调控细胞周期和凋亡促进宫颈癌进展。

Long noncoding RNA PITPNA-AS1 promotes cervical cancer progression through regulating the cell cycle and apoptosis by targeting the miR-876-5p/c-MET axis.

机构信息

Department of Obstetrics and Gynecology, Binzhou Medical University Hospital, Binzhou, 256603, China.

Department of Obstetrics and Gynecology, Binzhou Medical University Hospital, Binzhou, 256603, China.

出版信息

Biomed Pharmacother. 2020 Aug;128:110072. doi: 10.1016/j.biopha.2020.110072. Epub 2020 May 24.

Abstract

Cervical cancer is a common tumor type and a leading cause of tumor death among female in the world. However, the molecular mechanisms revealing the cervical cancer progression have not been fully investigated. Long noncoding RNA (LncRNA) PITPNA-AS1 is a newly found lncRNA, showing the promoting role in tumor growth. But its effects on cervical cancer development still remain unknown. In the study, we found that PITPNA-AS1 was markedly increased in human cervical cancer tissues and cell lines. PITPNA-AS1 over-expression elevated the proliferation of cervical cancer cells, whereas PITPNA-AS1 knockdown reduced the cell proliferation. Moreover, PITPNA-AS1 knockdown markedly accelerated the G0/G1 and reduced the G2/M phase transitions through decreasing the cyclin-dependent kinase (CDK)-2/4/6 and CyclinD1 expression levels. In addition, apoptosis was significantly induced by PITPNA-AS1 knockdown in cervical cancer cells. Importantly, PITPNA-AS1 was identified as the sponge of miR-876-5p, and a negative correlation was detected between PITPNA-AS1 and miR-876-5p in cervical cancer samples. Moreover, tyrosine-protein kinase MET (c-MET) was identified to be a down-streaming target gene of miR-876-5p in cervical cancer cells. PITPNA-AS1 meditated the effects of c-MET on the proliferation, apoptosis and cell cycle in cervical cancer cells by adsorbing miR-876-5p. In summary, targeting the PITPNA-AS1-associated signaling could be a therapeutic strategy for the treatment of cervical cancer.

摘要

宫颈癌是一种常见的肿瘤类型,也是全球女性肿瘤死亡的主要原因。然而,揭示宫颈癌进展的分子机制尚未得到充分研究。长链非编码 RNA (LncRNA) PITPNA-AS1 是一种新发现的 lncRNA,在肿瘤生长中表现出促进作用。但其对宫颈癌发展的影响仍不清楚。在研究中,我们发现 PITPNA-AS1 在人宫颈癌组织和细胞系中明显增加。PITPNA-AS1 的过表达可增强宫颈癌细胞的增殖,而 PITPNA-AS1 的敲低则降低了细胞增殖。此外,PITPNA-AS1 的敲低通过降低细胞周期蛋白依赖性激酶 (CDK)-2/4/6 和 CyclinD1 的表达水平,显著加速 G0/G1 期和减少 G2/M 期的转变。此外,PITPNA-AS1 的敲低可显著诱导宫颈癌细胞凋亡。重要的是,PITPNA-AS1 被鉴定为 miR-876-5p 的海绵,在宫颈癌样本中检测到 PITPNA-AS1 与 miR-876-5p 之间存在负相关。此外,酪氨酸蛋白激酶 MET (c-MET) 被鉴定为宫颈癌细胞中 miR-876-5p 的下游靶基因。PITPNA-AS1 通过吸附 miR-876-5p 介导 c-MET 对宫颈癌细胞增殖、凋亡和细胞周期的影响。总之,靶向 PITPNA-AS1 相关信号通路可能是治疗宫颈癌的一种治疗策略。

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