Huang Xuan, Zhu Jialei, Li Yueyan, Yu Yang, Tang Jing
Department of Pharmacy, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
Front Oncol. 2022 Aug 30;12:763480. doi: 10.3389/fonc.2022.763480. eCollection 2022.
Research on the mechanism and new targets of ovarian cancer is of great significance to reduce the high mortality and drug resistance of ovarian cancer. Human La protein has been found to be highly expressed in a variety of malignant tumors and plays a role in tumorigenesis and development through its RNA-binding function. However, its role and mechanism in ovarian cancer are not completely clear. The present study showed that La protein was highly expressed in serum and tissues of patients with ovarian cancer by ELISA and immunohistochemistry, and the high expression of La protein was associated with the increased degree of malignancy and poor prognosis by searching the KM plotter database. Interference of the La gene resulted in a significant decrease in the proliferation, migration, and invasion of ovarian cancer cells with growth block in the G1 phase and increasing apoptosis. By RNA binding protein immunoprecipitation, transcriptome sequencing, and proteomics, 14 downstream target genes were screened. The La protein might affect the protein expression of these 14 genes by binding with the mRNAs. Therefore, it played a role in the pathological process of ovarian cancer.
卵巢癌发病机制及新靶点的研究对于降低卵巢癌的高死亡率和耐药性具有重要意义。研究发现,人La蛋白在多种恶性肿瘤中高表达,并通过其RNA结合功能在肿瘤发生发展中发挥作用。然而,其在卵巢癌中的作用及机制尚不完全清楚。本研究通过ELISA和免疫组化显示,La蛋白在卵巢癌患者血清和组织中高表达,通过检索KM plotter数据库发现,La蛋白的高表达与恶性程度增加及预后不良相关。干扰La基因导致卵巢癌细胞的增殖、迁移和侵袭显著降低,细胞生长阻滞于G1期,凋亡增加。通过RNA结合蛋白免疫沉淀、转录组测序和蛋白质组学,筛选出14个下游靶基因。La蛋白可能通过与这些基因的mRNA结合影响其蛋白表达,进而在卵巢癌的病理过程中发挥作用。