PTOV1 promotes cisplatin-induced chemotherapy resistance by activating the nuclear factor kappa B pathway in ovarian cancer

Abstract

Chemotherapy resistance is a bottleneck for ovarian cancer treatment; therefore, revealing its regulatory mechanism is critical. In the present study, we found that prostate tumor overexpressed-1 (PTOV1) was upregulated significantly in ovarian cancer cells and tissues. Patients with high PTOV1 levels had a poor outcome. In addition, PTOV1 overexpression increased CDDP (cisplatin) resistance, while PTOV1 knockdown inhibited CDDP resistance, as determined using cell viability assays, apoptosis assays, and an animal model. Mechanistic analysis showed that PTOV1 increased nuclear factor kappa B (NF-κB) pathway activity, reflected by increased nuclear translocation of its p65 subunit and the phosphorylation of inhibitor of nuclear factor kappa-B kinase subunits alpha and beta, which are markers of NF-κB pathway activation. Inhibition of the NF-κB pathway in PTOV1 -overexpressing ovarian cancer cells increased CDDP-induced apoptosis, suggesting that PTOV1 promoted chemotherapy resistance by activating the NF-κB pathway. In summary, we identified PTOV1 as a prognostic factor for patients with ovarian cancer. PTOV1 might be a target for inhibition of chemotherapy resistance.

SIAH1-Mediated RPS3 Ubiquitination Contributes to Chemosensitivity in Epithelial Ovarian Cancer

“…As reported, RPS3 interacts with the p65 subunit of nuclear factor kappa B (NF-κB) through its K homology domain, which results in NF-κB-induced transcriptional activation (38)(39)(40). NF-κB adjusts the expression of genes (PTOV1, c-Myb, TRIM52) (41)(42)(43) related to numerous processes that play a pivotal role in the development and progression of cancer, such as proliferation, migration and apoptosis (44). Many ndings have indicated that NF-κB pathway activation promotes ovarian cancer chemotherapy resistance (41)(42)(43).…”

“…NF-κB adjusts the expression of genes (PTOV1, c-Myb, TRIM52) (41)(42)(43) related to numerous processes that play a pivotal role in the development and progression of cancer, such as proliferation, migration and apoptosis (44). Many ndings have indicated that NF-κB pathway activation promotes ovarian cancer chemotherapy resistance (41)(42)(43).…”

PTOV1 is a Prognostic Biomarker and Correlated with Poor Progression in Colorectal Cancer

“…Likewise, other studies show that PTOV1 promotes prostate cancer invasion and growth by counteracting Notch pathway signaling and promoting the translation of JUN (encoding C-Jun) [8]. Moreover, more and more studies showed that PTOV1 as a prognostic factor for patients with many cancers such as ovarian cancer, nonsmall cell lung cancer, urothelial carcinoma and other cancer [9][10][11][12]. And also, PTOV1 might be a target for inhibition of chemotherapy resistance [9,10,13].…”

Contributions of NFKB1 ‐94insertion/deletion ATTG polymorphism to the susceptibility of gastrointestinal cancers: A meta‐analysis

“… 25 NF‐κB expression is strictly regulated in normal cells, but it is generally overexpressed in many cancer cells. 26 Upregulation of NF‐κB has been observed in several types of cancer, including hepatocellular carcinogenesis, 27 , 28 colon cancer, 29 breast cancer, 30 ovarian cancer 31 and glioma cancer. 32 Multiple number of NFKB1 gene SNPs were investigated in the implication of cancer.…”