TEX10 Promotes the Tumorigenesis and Radiotherapy Resistance of Urinary Bladder Carcinoma by Stabilizing XRCC6

Abstract

Urinary bladder carcinoma refers to the commonest carcinoma with weak prognostic result for the patient as impacted by the limited treatment possibilities and challenging diagnosing process. Nevertheless, the molecular underpinning of bladder carcinoma malignant progression is still not clear. As a novel core part of pluripotency circuitry, testicular expression 10 (TEX10) plays an actively noticeable effect on reprogramming, early embryo development, and embryonic stem cell self-renewal. Nevertheless, TEX10 expressions and functions within bladder carcinoma are still not known. The present work is aimed at revealing TEX10 expression and biological function within urinary bladder carcinoma and elucidating the potential mechanisms. Results showed that TEX10 is abundant in urinary bladder carcinoma, and its protein level was related to poor disease-free survival in a positive manner. Reduced TEX10 level inhibited urinary bladder carcinoma cell proliferating process and metastasis in vitro and xenograft tumorigenicity in vivo. Notably, TEX10 might regulate carcinoma cell proliferating process and metastasis via XRCC6, thereby controlling the signaling of Wnt/β-catenin and DNA repair channel. Moreover, TEX10 gene knockout reduced the radiotherapy resistance of urinary bladder carcinoma. In brief, this work revealed that TEX10 could exert a significant carcinogenic effect on urinary bladder carcinoma tumorigenesis and radiotherapy resistance through the activation of XRCC6-related channels. Accordingly, targeting TEX10 is likely to offer a novel and feasible therapeutically related strategy for inhibiting urinary bladder carcinoma tumorigenicity.

Tex10 interacts with STAT3 to regulate hepatocellular carcinoma growth and metastasis

“…These results suggest a crucial role of Tex10 in HCC aggressiveness. Consistent with our results, a previous study showed that Tex10 promotes cell proliferation by stabilizing XRCC6 in urinary bladder carcinoma 7 . Furthermore, Tex10 was also reported to promote colorectal cancer cell proliferation by activating NF‐κB 6 …”

“…Testis expressed 10 (Tex10), a core component of the pluripotency network, plays a critical role in embryonic stem cell self‐renewal and pluripotency and is enriched in association with super‐enhancers in a Sox2‐dependent manner 4 . Furthermore, several studies have identified Tex10 as a putative oncogene that is highly expressed in HCC, esophageal squamous cell carcinoma, colorectal cancer, and urinary bladder carcinoma 5–7 . In our previous study, Tex10 was shown to activate signal transducer and activator of transcription 3 (STAT3) signaling and subsequently promote cancer stem cell properties in HCC 5 .…”

“…4 Furthermore, several studies have identified Tex10 as a putative oncogene that is highly expressed in HCC, esophageal squamous cell carcinoma, colorectal cancer, and urinary bladder carcinoma. [5][6][7] In our previous study, Tex10 was shown to activate signal transducer and activator of transcription 3 (STAT3) signaling and subsequently promote cancer stem cell properties in HCC. 5 Moreover, Tex10 has been shown to regulate stemness and epithelial-mesenchymal transition (EMT) in cancer cells via the Wnt/β-catenin pathway.…”

From multi-omics data to the cancer druggable gene discovery: a novel machine learning-based approach

“…In addition, studies have shown that Tex10 plays a decisive oncogenic role in HCC tumorigenesis by activating the STAT3 signaling pathway and promoting chemoresistance to maintain cancer stem cell properties. Therefore, targeting Tex10 may provide a novel and effective therapeutic strategy to inhibit the tumorigenicity of advanced HCC [38, 39, 40]. The above results suggest that DF-CAGE helps find cancer druggable genes beyond the known driver genes, which have received relatively little attention in previous studies.…”

Biology of Cancer-Testis Antigens and Their Therapeutic Implications in Cancer

“…We further showed that GAGE, specifically the GAGE12 variant, augmented chromatin dynamics in cancer cells allowing for increased accessibility of DNA damage repair factors, which, upon induction of DNA damage, promoted more efficient DNA repair, protecting cells from DNA-damage-induced apoptosis [ 73 ]. Another study also demonstrated that TEX10 (testis expressed 10) promoted radioresistance in urinary bladder carcinoma by stabilising XRCC6 (x-ray repair cross complementing 6), a key factor required for efficient NHEJ upon induction of DNA damage by agents such as ionising radiation [ 111 ].…”