Targeting TRIP13 for overcoming anticancer drug resistance (Review).

Cancer is one of the greatest dangers to human wellbeing and survival. A key barrier to effective cancer therapy is development of resistance to anti­cancer medications. In cancer cells, the AAA+ ATPase family member thyroid hormone receptor interactor 13 (TRIP13) is key in promoting treatment resistance. Nonetheless, knowledge of the molecular processes underlying TRIP13­based resistance to anticancer therapies is lacking. The present study evaluated the function of TRIP13 expression in anticancer drug resistance and potential methods to overcome this resistance. Additionally, the underlying mechanisms by which TRIP13 promotes resistance to anticancer drugs were explored, including induction of mitotic checkpoint complex surveillance system malfunction, promotion of DNA repair, the enhancement of autophagy and the prevention of immunological clearance. The effects of combination treatment, which include a TRIP13 inhibitor in addition to other inhibitors, were discussed. The present study evaluated the literature on TRIP13 as a possible target and its association with anticancer drug resistance, which may facilitate improvements in current anticancer therapeutic options.

TRIP13 overexpression in hepatocellular carcinoma: implications for poor prognosis and immune cell infiltration.

PURPOSE: The overexpression of TRIP13 has been observed in many types of cancer and has been identified as an oncogene. However, its role in hepatocellular carcinoma (HCC) has not been extensively studied. This study aimed to investigate the expression of TRIP13 in HCC and its impact on immune cell infiltration and prognosis. METHODS: We analyzed TCGA and GSE62232 datasets to assess TRIP13 expression in HCC. Kaplan-Meier and subgroup analysis were performed to examine the correlation between TRIP13 expression and HCC. Univariate and Cox regression analysis were conducted to determine the predictive value of TRIP13 in assessing patient outcomes. A nomogram was developed using TRIP13 mRNA expression to predict HCC prognosis. TRIP13 expression was validated using immunohistochemistry in our patient cohort. Survival and subgroup analyses were conducted to investigate the role of TRIP13 in HCC prognosis. RESULTS: The results indicated that TRIP13 upregulation in HCC was a strong independent predictor of poor outcome, as determined by Kaplan-Meier and Cox regression analyses. A high AUC value of 0.982 from ROC curves suggested that TRIP13 upregulation could serve as a reliable diagnostic indicator for HCC. The immunohistochemical validation of TRIP13 expression in the patient cohort confirmed its prognostic significance, and high TRIP13 expression was found to be associated with increased infiltration of Th2 cells and decreased infiltration of neutrophils, Th17 cells, and dendritic cells. CONCLUSION: These findings suggest that TRIP13 could be a potential prognostic biomarker for HCC.

Examining the expression and correlation of trip13 and angpt1 in small cell lung cancer: a professional exploration with an analogy to football players

This professional exploration delves into the intricate realm of thyroid hormone receptor interactor 13 (TRIP13) and angiopoietin-1 (ANGPT1) within the context of small cell lung cancer (SCLC). Drawing parallels to the precision and teamwork exemplified by football players on the field, we meticulously investigate the expression patterns and correlations of these molecular players in the complex landscape of SCLC. Our study encompassed a cohort of 78 SCLC patients treated at our institution between January 2015 and April 2017. Through rigorous immunohistochemical staining, we scrutinized the expression profiles of TRIP13 and ANGPT1 within tumor tissues, seeking to unravel their associations with clinicopathological characteristics and progression-free survival. Noteworthy findings emerged from our analysis. We observed significantly elevated positive expression rates of TRIP13 in SCLC tissues with lower differentiation levels and liver metastases, highlighting the analogy to football players' precise maneuvers. Similarly, ANGPT1 exhibited markedly increased positive expression rates in cases with larger tumor diameters, lower differentiation, and liver metastases, akin to a coordinated football team's collective effort. Our professional exploration uncovered a compelling positive correlation between the expression levels of TRIP13 and ANGPT1 in SCLC, akin to the synergy seen among football players on the field. This molecular partnership shed light on an intriguing aspect of SCLC's pathophysiology. The impact on progression-free survival time further emphasized the clinical relevance of TRIP13 and ANGPT1 in SCLC. Patients expressing both TRIP13 and ANGPT1 or either molecule alone experienced significantly shorter mean progression-free survival times, akin to the swift tactics and strategies employed by football players in a high-stakes game. (AU)

lncRNA LINC00308 acts as a competing endogenous RNA to promote the proliferation and invasion of prostate cancer PC3 cell through regulating the miR-361-5p/TRIP13 axis / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the effect of long non coding RNA (lncRNA) LINC00308 on proliferation, invasion and migration of prostate cancer cells and its related mechanism. Methods: lncRNAs and mRNAs differentially expressed in prostate cancer tissues and adjacent control tissues were screened by gene chip, and LINC00308 and TRIP13 (thyroid hormone receptor interactor13) were identified as the research objects. The effects of LINC00308 on the proliferation, invasion and migration of prostate cancer cells were detected by MTT assay, plate cloning, Transwell and scratch test. The above effects were verified in nude mice xenografts. The effect of LINC00308 on expression of TRIP13 in tumor tissues and cancer cells was detected by Western blotting and immunohistochemistry. Bioinformatics analysis, RIP (RNA immunoprecipitation), qPCR and Double luciferase gene reporter experiments were used to predict and explore the interaction mechanism between miR-361-5p and LINC00308 as well as TRIP13, and plate cloning and Transwell invasion test were used to verify the biological behaviors of cancer cells. Results: Both the microarray results and qPCR confirmed that the expressions of LINC00308 (P<0.01) and TRIP13 (P<0.05) were abnormally high in prostate cancer tissues and four cell lines; cell function test results showed that overexpression of LINC00308 could promote the proliferation, invasion and migration of prostate cancer PC3 cells (all P<0.05), while down-regulation of LINC00308 in prostate cancer cells had the opposite effect. In nude mice. LINC00308 could promote the tumorigenesis of prostate cancer cells in vivo, and increase the expression of TRIP13 both in vivo and in vitro (P<0.05). Bioinformatics analysis, RIP, qPCR and Double luciferase gene reporter results confirmed that miR-361-5p could bind to 3'-UTR of LINC00308 and TRIP13 respectively, and LINC00308 could act as a competing endogenous RNA (ceRNA) by sponging miR-361-5p to regulate the expression of TRIP13. In addition, MTT, plate cloning and Transwell assay confirmed the regulatory interaction among LINC00308 miR-361-5p and TRIP13 from the levels of proliferation, colony formation and invasion in cancer cells. Conclusion: LINC00308, which is abnormally highly expressed in prostate cancer tissues and cells, can inhibit the expression of miR-361-5p and enhance the expression of TRIP13 by exerting its ceRNA function, thus promoting the proliferation, invasion and migration of prostate cancer.

Thyroid hormone receptor interactor 13 (TRIP13) overexpression associated with tumor progression and poor prognosis in lung adenocarcinoma.

Thyroid hormone receptor interactor 13 (TRIP13) is an AAA+-ATPase that plays a key role in mitotic checkpoint complex inactivation and is associated with the progression of several cancers. However, its role in lung adenocarcinogenesis remains unknown. Here, we report that TRIP13 is highly overexpressed in multiple lung adenocarcinoma cell lines and tumor tissues. Clinically, TRIP13 expression is positively associated with tumor size, T-stage, and N-stage, and Kaplan-Meier analysis revealed that heightened TRIP13 expression is associated with lower overall survival. TRIP13 promotes lung adenocarcinoma cell proliferation, clonogenicity, and migration while inhibiting apoptosis and G2/M phase shift in vitro. Accordingly, TRIP13-silenced xenograft tumors displayed significant growth inhibition in vivo. Bioinformatics analysis demonstrated that TRIP13 interacts with a protein network associated with dsDNA break repair and PI3K/Akt signaling. TRIP13 upregulatesAktSer473 and downregulatesAktThr308/mTORSer2448activity, which suppresses accurate dsDNA break repair. TRIP13 also downregulates pro-apoptotic BadSer136 and cleaved caspase-3 while upregulating survivin. In conclusion, heightened TRIP13 expression appears to promote lung adenocarcinoma tumor progression and displays potential as a therapeutic target or biomarker for lung adenocarcinoma.