Acta Biochim Biophys Sin (Shanghai). 2023 Apr 28;55(4):623-632. doi: 10.3724/abbs.2023069.
Cervical cancer continues to be a concern, and the prognosis of locally advanced cervical cancer remains poor. was previously identified as a potential oncogene and regulator of tumor apoptosis. In this study, we aim to further elucidate the underlying mechanisms of gene in the regulation of cervical cancer apoptosis. First, we identify as an upregulated gene in -silenced cervical cancer cells, and inhibition of reverses knockdown-induced apoptosis. Further study reveals that regulates cell apoptosis in a mitochondrial-dependent manner with a redistribution of mitochondrial membrane potential and intracellular Ca levels. However, the analysis of the STRING database and our experimental results show that has little effect on cervical cancer progression and survival. Further mechanistic study demonstrates that and silencing inhibits apoptosis by activating p53. Meanwhile, the knockdown of enhances the chemosensitivity of cervical cancer cells by strengthening paclitaxel-induced apoptosis. Based on the above results, the IMPA2/AIFM2/p53 pathway may be a new molecular mechanism for paclitaxel treatment of cervical cancer and an effective strategy to enhance the sensitivity of cervical cancer cells to paclitaxel. Our findings display a novel function of in regulating cell apoptosis and paclitaxel resistance mediated by a disturbance of and expression, potentially making it a novel therapeutic target for cervical cancer treatment.
宫颈癌仍然是一个关注点，局部晚期宫颈癌的预后仍然很差。IMP3 先前被鉴定为一种潜在的癌基因和肿瘤细胞凋亡的调节剂。在这项研究中，我们旨在进一步阐明 基因在调控宫颈癌细胞凋亡中的潜在机制。首先，我们鉴定出在沉默的宫颈癌细胞中上调的 基因，并且抑制 基因可逆转 基因敲低诱导的细胞凋亡。进一步的研究表明， 基因以线粒体依赖性方式调节细胞凋亡，伴有线粒体膜电位和细胞内 Ca2+水平的重新分布。然而，STRING 数据库的分析和我们的实验结果表明，IMP3 对宫颈癌的进展和生存几乎没有影响。进一步的机制研究表明，IMP3 和 AIFM2 基因沉默通过激活 p53 抑制细胞凋亡。同时，IMP3 基因的敲低通过增强紫杉醇诱导的细胞凋亡增强了宫颈癌细胞的化疗敏感性。基于上述结果，IMP2/AIFM2/p53 通路可能是紫杉醇治疗宫颈癌的新分子机制，也是增强宫颈癌细胞对紫杉醇敏感性的有效策略。我们的研究结果显示了 基因在调节细胞凋亡和紫杉醇耐药性方面的新功能，可能使其成为宫颈癌治疗的新的治疗靶点。
