RETRACTED: OTUB2 Promotes Homologous Recombination Repair Through Stimulating Rad51 Expression in Endometrial Cancer

Abstract

Genetic instability, raised from dysregulation of DNA repair, is involved in tumor development. OTUB2 (ovarian tumor domain protease domain-containing ubiquitin aldehyde-binding protein 2), which is responsible for DNA double-strand break (DSB), is implicated in carcinogenesis of various tumors. The effect of OTUB2 on endometrial cancer progression was then investigated. First, OTUB2 was found to be upregulated in endometrial cancer tissues and cell lines, and was closely associated with overall survival of endometrial cancer patients. Cell Counting Kit-8 and flow cytometry assay results revealed that overexpression of OTUB2 enhanced cell viability of endometrial cancer cells, while knockdown of OTUB2 inhibited cell viability. Moreover, as demonstrated by promoting cell viability and suppression of cell apoptosis, cisplatin-induced cell damage was reversed by OTUB2. Mechanistically, OTUB2 could activate Yes-associated protein/transcriptional co-activator with PDZ-binding motif (TAZ) to promote homologous recombination repair via depletion of γH2AX (phosphorylation of histone H2AX) and accumulation of Rad51. In vivo xenograft model also showed that silence of OTUB2 suppressed the growth of endometrial cancer and increased tumor sensitivity to antitumor drugs. In conclusion, OTUB2 promoted homologous recombination repair in endometrial cancer via YAP/TAZ-mediated Rad51 expression, providing a potential therapeutic target for endometrial cancer.

OTUB2 Regulates YAP1/TAZ to Promotes the Progression of Esophageal Squamous Cell Carcinoma

“…It has also been reported that OTUB2 promotes homologous recombination repair of endometrial carcinoma through YAP/TAZ mediated Rad51 expression, which provides a potential therapeutic target for endometrial carcinoma. Silencing of OTUB2 can inhibit the growth of endometrial cancer and increases the sensitivity of tumor to anti-tumor drugs [ 8 ]. In the HCC cell line, knocking-down OTUB2 expression can significantly inhibit the growth of liver cancer cells [ 9 ].…”

“…OTUB2 is a dihydroubiquitase, a member of the ovarian tumor domain (OTU) family with effects on various biological activities of the body [ 3 , 4 ]. Some researchers have found that OTUB2 promotes the development of breast cancer [ 5 ], non-small cell lung cancer [ 6 ], thyroid papilloma cancer [ 7 ], endometrial cancer [ 8 ], and liver cancer [ 9 ]. Yes-associated protein (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ) are core factors located downstream of the Hippo signaling pathway.…”

The Emerging Role of OTUB2 in Diseases: From Cell Signaling Pathway to Physiological Function

“…Therefore, OTUB2, as an intermediate molecule, both undertakes the downstream effects of RAS mutations and triggers YAP/TAZ-mediated oncogene expression based on its deubiquitination function (K48), forming a chain reaction and worsening cancer progression. On this basis, the overexpression of recombination protein A (Rad51) in endometrial cancer is a representative example of YAP/TAZ-mediated gene expression ( Wan et al, 2020 ). The up-regulation of Rad51 protein can not only lead to drug resistance of cancer cells but also promote cell growth and proliferation ( Klein, 2008 ; Chen et al, 2017 ).…”

“…Similarly, overexpression of OTUB2 in endometrial carcinoma can indirectly increase Rad51 expression by interacting with YAP/TAZ to promote HR ( Wan et al, 2020 ). However, this HR in endometrial cancer tissues seems to be pathological ( Wan et al, 2020 ).…”

“…Similarly, overexpression of OTUB2 in endometrial carcinoma can indirectly increase Rad51 expression by interacting with YAP/TAZ to promote HR ( Wan et al, 2020 ). However, this HR in endometrial cancer tissues seems to be pathological ( Wan et al, 2020 ). Cancer cells rely on HR to maintain their genetic stability and avoid apoptosis, which generally aggravates cancer progression.…”