Department of Obstetrics and Gynecology, Binzhou Medical University Hospital, Binzhou, 256603, China.
Department of Obstetrics and Gynecology, Binzhou Medical University Hospital, Binzhou, 256603, China.
Biomed Pharmacother. 2020 Aug;128:110072. doi: 10.1016/j.biopha.2020.110072. Epub 2020 May 24.
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.
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。