Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, 350014 Fuzhou, Fujian, China.
Department of Obstetrics and Gynecology, Shengli Clinical Medical College of Fujian Medical University and Fujian Provincial Hospital, 350001 Fuzhou, Fujian, China.
Front Biosci (Landmark Ed). 2024 Aug 19;29(8):289. doi: 10.31083/j.fbl2908289.
Cervical cancer is the most common gynecological malignancy in the world and seriously threatens to women's lives and health. Polypyrimidine tract binding protein 1 (PTBP1), as an important splicing factor, has been identified as a proto-oncogene in several cancers, but its role and mechanism in cervical cancer remain poorly understood. Thus, our aim is to explore the impact of PTBP1 on proliferation, migration, apoptosis of cervical cancer cells, and its underlying mechanisms.
The biological functions in cervical cancer cells were determined using small interfering RNA (siRNA), agonist, Cell Counting Kit-8 (CCK-8), transwell, migration test, western blot, real-time-PCR, immunohistochemistry and immunofluorescence, respectively.
The results indicated that PTBP1 was highly expressed in cervical cancer patients and cervical cancer cell lines compared to the normal group. Moreover, PTBP1 silencing significantly inhibited cell proliferation, and migration in both HeLa and SiHa cells. The PTBP1 silencing also induced mitochondrial apoptosis through upregulating Bax and mitochondrial apoptotic protein Cytochrome C, and downregulating B-Cell Leukemia/Lymphoma 2 (Bcl2) protein. Additionally, PTBP1 silencing induced autophagy by downregulating Sequestosome I (p62) and upregulating the ratio of Light chain 3-Ⅱ/Light chain 3-Ⅰ (LC3-Ⅱ/LC3-Ⅰ). Mechanistically, we found that the Phosphoinositide 3-kinase (PI3K) agonist reversed the changes induced by PTBP1 silencing.
Overall, PTBP1 silencing can induce cervical cancer cells apoptosis mainly through PI3K/AKT pathway and protective autophagy. This study provides preliminary evidence for PTBP1 as a therapeutic target or prognostic marker for cervical cancer.
宫颈癌是全球最常见的妇科恶性肿瘤，严重威胁着女性的生命和健康。多嘧啶核苷酸结合蛋白 1（PTBP1）作为一种重要的剪接因子，已在几种癌症中被鉴定为原癌基因，但它在宫颈癌中的作用和机制仍知之甚少。因此，我们的目的是探讨 PTBP1 对宫颈癌细胞增殖、迁移、凋亡的影响及其潜在机制。
采用小干扰 RNA（siRNA）、激动剂、细胞计数试剂盒（CCK-8）、Transwell、迁移试验、Western blot、实时 PCR、免疫组织化学和免疫荧光分别检测 PTBP1 在宫颈癌细胞中的生物学功能。
结果表明，与正常组相比，PTBP1 在宫颈癌患者和宫颈癌细胞系中高表达。此外，PTBP1 沉默显著抑制了 HeLa 和 SiHa 细胞的增殖和迁移。PTBP1 沉默还通过上调 Bax 和线粒体凋亡蛋白 Cytochrome C，下调 B 细胞白血病/淋巴瘤 2（Bcl2）蛋白诱导线粒体凋亡。此外，PTBP1 沉默通过下调自噬受体 Sequestosome I（p62）和上调微管相关蛋白 1 轻链 3-Ⅱ/微管相关蛋白 1 轻链 3-Ⅰ（LC3-Ⅱ/LC3-Ⅰ）的比值诱导自噬。机制上，我们发现磷脂酰肌醇 3-激酶（PI3K）激动剂逆转了 PTBP1 沉默引起的变化。
总之，PTBP1 沉默可以通过 PI3K/AKT 通路和保护性自噬诱导宫颈癌细胞凋亡。本研究为 PTBP1 作为宫颈癌治疗靶点或预后标志物提供了初步证据。
