Bio-Medical Research Center, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China.
Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou, 730000, China.
J Cancer Res Clin Oncol. 2022 Dec;148(12):3475-3484. doi: 10.1007/s00432-022-04170-3. Epub 2022 Jul 27.
Splicing factor poly(rC)-binding protein 1 (PCBP1) is a novel tumor suppressor that is downregulated in several cancers thereby regulating tumor formation and metastasis. However, the involvement of PCBP1 in apoptosis of cancer cells and the molecular mechanism remains elusive. On this basis, we sought to investigate the role of splicing factor PCBP1 in the apoptosis in human cervical cancer cells.
To investigate PCBP1 functions in vitro, we overexpressed PCBP1 in human cervical cancer cells. A series of cytological function assays were employed to study to the role of PCBP1 in cell proliferation, cell cycle arrest and apoptosis.
Overexpression of PCBP1 was found to greatly repress proliferation of HeLa cells in a time-dependent manner. It also induced a significant increase in G2/M phase arrest and apoptosis. Furthermore, overexpressed PCBP1 favored the production of long isoforms of p73, thereby inducing upregulated ratio of Bax/Bcl-2, the release of cytochrome c and the expression of caspase-3.
Our results revealed that PCBP1 played a vital role in p73 splicing, cycle arrest and apoptosis induction in human cervical carcinoma cells. Targeting PCBP1 may be a potential therapeutic strategy for cervical cancer therapy.
剪接因子多聚（rC）结合蛋白 1（PCBP1）是一种新型的肿瘤抑制因子，在几种癌症中下调，从而调节肿瘤的形成和转移。然而，PCBP1 在癌细胞凋亡中的作用及其分子机制仍不清楚。在此基础上，我们试图研究剪接因子 PCBP1 在人宫颈癌细胞凋亡中的作用。
为了研究体外 PCBP1 的功能，我们在人宫颈癌细胞中过表达了 PCBP1。采用一系列细胞学功能测定来研究 PCBP1 在细胞增殖、细胞周期阻滞和细胞凋亡中的作用。
过表达 PCBP1 被发现能在时间依赖性的方式显著抑制 HeLa 细胞的增殖。它还诱导 G2/M 期阻滞和凋亡的显著增加。此外，过表达的 PCBP1 有利于 p73 的长异构体的产生，从而诱导 Bax/Bcl-2 比值上调、细胞色素 c 的释放和 caspase-3 的表达。
我们的结果表明，PCBP1 在人宫颈癌细胞中 p73 剪接、周期阻滞和凋亡诱导中发挥着重要作用。靶向 PCBP1 可能是宫颈癌治疗的一种潜在的治疗策略。
