Abstract. Ovarian cancer is the most common cause of gynecological cancer-related mortality. Serine/threonine protein phosphatase 5 (PP5, PPP5C) has been recognized to be involved in the regulation of multiple cellular signaling cascades that control diverse cellular processes, including cell growth, differentiation, proliferation, motility and apoptosis. In this study, to evaluate the functional role of PP5 in ovarian cancer cells, lentivirus-mediated RNA interference (RNAi) was applied to silence PPP5C in the human ovarian cancer cell line CAOV-3. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell colony forming ability was measured by colony formation. Cell cycle progression was determined by propidium iodide staining and flow cytometry. The results demonstrated that lentivirus-mediated RNAi specifically suppressed the expression of PPP5C at the mRNA and protein levels in CAOV-3 cells. Further investigations revealed that PP5 knockdown significantly inhibited the proliferation and colony formation of CAOV-3 cells. Moreover, the cell cycle of CAOV-3 cells was arrested at the G0/G1 phase following PP5 knockdown. This study highlights the crucial role of PP5 in promoting ovarian cancer cell proliferation, and provides a foundation for further study into the clinical potential of lentiviral-mediated delivery of PP5 RNAi therapy for the treatment of ovarian cancer. IntroductionOvarian cancer is the most common invasive malignancy of the female genital tract in the USA, with an estimated 22,240 cases diagnosed annually. Approximately 14,030 females succumb every year to ovarian cancer, representing the most common cause of mortality among females with gynecological malignancies (1). Surgical resection and platinum-based combination regimens offer a modest but significant survival advantage in ovarian cancer patients with advanced or metastatic disease, although most patients eventually experience disease progression (2). These data highlight the need to identify new approaches that, along with the current treatments, may assist in bringing about a better outcome for ovarian cancer patients.Protein kinases and phosphatases work together to control cellular processes and signaling pathways (3,4). Although much more is known about protein kinases and their relevant substrates compared with protein phosphatases (5-7), the significance of studying protein phosphatase enzymes and their targets has been demonstrated for disease states attributed in part to malfunctioning protein phosphatase enzymes (8). Protein phosphatase 5 (PP5; gene name, PPP5C) is a ubiquitously expressed serine/threonine protein phosphatase related to PP1, PP2A and PP2B (9). Structural analysis has revealed that PP5 contains a C-terminal catalytic domain and three N-terminal tetratricopeptide repeats (TPRs) that are unique in the phosphoprotein phosphatase family (10). PP5 is auto-inhibited by intramolecular interactions with its TPR domain (11).PP5 has been implicated in numerous cellular processe...
c1q/TnF-α-related protein 9 (cTrP9) is downregulated in gestational diabetes mellitus (GdM) and may exert a protective effect against GdM, although its mechanism of action is yet to be elucidated. To investigate the specific role of cTrP9 in GdM, the human placental trophoblast cell line HTr8/SVneo was treated with high glucose (HG) to simulate the environment of GdM in vitro. The effects of cTrP9 on the HTr8/SVneo cells and endoplasmic reticulum (er) stress were analyzed before and after cTrP9 overexpression using reverse transcription-quantitative Pcr and western blotting. The results obtained demonstrated that cTrP9 alleviated er stress in the trophoblast cell line. after treating with the er-stress inducer tunicamycin, cell viability was investigated by performing cell counting Kit-8, Tunel and western blotting assays, which revealed that cTrP9 increased the activity of HTr8/SVneo cells induced by HG through the alleviation of er stress. Subsequently, eliSa and western blotting assay results demonstrated that cTrP9 inhibited HG-induced inflammation of the HTR8/SVneo cells by the reduction in ER stress. Finally, the detection of reactive oxygen species, nitric oxide (NO) synthase and NO levels confirmed that CTRP9 inhibited the oxidative stress of HTr8/SVneo cells induced by HG through the reduction of er stress. collectively, the results of the present study suggested that cTrP9 may decrease trophoblast cell damage caused by HG through the suppression of er stress, and therefore, cTrP9 may potentially be a therapeutic target in the treatment of GdM.
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