Elevated Expression of Thyroid Hormone Receptor-Interacting Protein 13 Drives Tumorigenesis and Affects Clinical Outcome

Wang, Dazhi; Zhang, Mengxi; Fufeng, Chen; Yan, Meixing

doi:10.2217/bmm-2016-0169

Cited by 25 publications

(19 citation statements)

References 26 publications

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“…TRIP13 was originally recognized as a participant in meiotic recombination, spindle assembly checkpoint, and DNA repair [15][16][17]. Actually, as a AAA ATPase, which can facilitate the assembly or degradation of protein complexes, TRIP13 has been reported to be significantly up-regulated in multiple types of tumors and involved in tumorigenesis by binding various proteins [18,19]. Bannerjee and his colleagues first verified that TRIP13 is an oncogene and demonstrated that it induces chemoresistance in head and neck cancer by interacting with the DNA-PK complex to enhance non-homologous end joining [17].…”

Section: Discussionmentioning

confidence: 99%

Elevated TRIP13 drives the AKT/mTOR pathway to induce the progression of hepatocellular carcinoma via interacting with ACTN4

Zhu

Wei

Zhang

et al. 2019

J Exp Clin Cancer Res

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Background: ATPase associated with a variety of cellular activities (AAA ATPase) family members are closely linked to tumor formation and progression. However, their roles in hepatocellular carcinoma (HCC) largely remain unclear. Methods: Bioinformatic analyses of public databases were used to excavate the potential AAA ATPases that may contribute to HCC, and thyroid hormone receptor interactor 13 (TRIP13) was selected to following researches because of its most prominently differential expression. Western blot, qRT-PCR and immunohistochemistry were used to detect the expression of TRIP13 in HCC tissues, and then the relationship between TRIP13 expression and clinicopathological parameters were evaluated. Finally, its functions and potential mechanisms were investigated through a series gain-and loss-of-function strategies both in vitro and in vivo. Results: TRIP13 was significantly overexpressed in HCC tissues and high level of TRIP13 was closely correlated with a worse clinical outcome. Functionally, elevated TRIP13 facilitated cell proliferation, migration, invasion, and promoted cellular epithelial-mesenchymal transition (EMT) in vitro, while promote tumor growth and lung metastasis in vivo. Mechanistically, TRIP13 interacted with ACTN4 and positively regulated its expression, thus activating the AKT/mTOR pathway to drive tumor progression. Moreover, miR-192-5p served as an upstream regulator of TRIP13 by directly binding to TRIP13 mRNA 3′ UTR, which may partially explain the high expression of TRIP13 in HCC. Conclusion: Our findings identified TRIP13 as a promising candidate oncogene in HCC, and TRIP13 induced cell migration, invasion and metastasis of HCC through the AKT/mTOR signaling via interacting with ACTN4.

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Section: Discussionmentioning

confidence: 99%

Elevated TRIP13 drives the AKT/mTOR pathway to induce the progression of hepatocellular carcinoma via interacting with ACTN4

Zhu

Wei

Zhang

et al. 2019

J Exp Clin Cancer Res

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“…TRIP13 has been suggested to be overexpressed in multiple tumors and function as oncogene in carcinogenesis. 14 Interestingly, we observed that TINCR expression was markedly negatively correlated with TRIP13 mRNA expression in 374 prostate cancer tissue samples from TCGA database ( r =−0.554, P <0.001, Figure 3A ). Furthermore, the relationship of TINCR expression with TRIP13 mRNA and protein was explored in prostate cancer tissues.…”

Section: Resultsmentioning

confidence: 90%

LncRNA TINCR is associated with clinical progression and serves as tumor suppressive role in prostate cancer

Dong¹,

Ding²,

Li³

et al. 2018

CMAR

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IntroductionTerminal differentiation-induced non-coding RNA (TINCR) has been suggested to have aberrant expression in multiple human cancers, and functions as tumor suppressor or promoter in various types of human tumors depending on the specific cancer types. The expression status and biological function of TINCR in prostate cancer is still unknown.Materials and methodsIn our study, we detected TINCR expression in prostate cancer tissue samples and cell lines, and analyzed the association between TINCR expression and clinical parameters in 160 prostate cancer patients. Moreover, we conducted gain-of-function and loss-of-function studies in prostate cancer cell to explore the biological function and molecular mechanism of TINCR.ResultsIn our results, low-expression TINCR was observed in prostate cancer, and correlated with advanced clinical T stage, lymph node involvement, distant metastasis, high Gleason score and poor prognosis in prostate cancer patients. Moreover, levels of TINCR expression were negatively associated with TRIP13 mRNA and protein expressions in prostate cancer tissues, and negatively regulated the TRIP13 mRNA and protein expressions in prostate cancer cell lines. TINCR inhibits prostate cancer cell proliferation, migration and invasion via suppressing TRIP13 expression.ConclusionTINCR plays a tumor suppressive role in regulating prostate cancer cell proliferation, migration and invasion through modulating TRIP13 expression.

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“…TRIP13 is identified as an oncogene, whose overexpression can lead to many human cancers. A large number of studies suggested that TRIP13 gene is highly expressed in head and neck cancer, prostate cancer, lung cancer and breast cancer tissues and is closely associated with colorectal cancer, gastric cancer [16, 21, 23–26].…”

Section: Introductionmentioning

confidence: 99%

Silencing TRIP13 inhibits cell growth and metastasis of hepatocellular carcinoma by activating of TGF-β1/smad3

Yao

Zhang

et al. 2018

Cancer Cell Int

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BackgroundTRIP13 is highly expressed in several cancers and is closely connected with cancer progression. However, its roles on the growth and metastasis of hepatocellular carcinoma (HCC), and the underlying mechanism are still unclear.MethodsCombining bioinformatics with previous studies, the correlation between TRIP13 and HCC was predicted. TRIP13 expressions from 52 HCC patients and several cell lines were determined. The effects of silencing TRIP13 on cell viability, apoptosis, migration and invasion were respectively detected using CCK-8, flow cytometry and Transwell. qRT-PCR and western blot were performed to reveal associated mechanism. A HCC model was established in BALB/c-nu mice by transplanting HepG2 cells. TRIP13 protein expression and apoptosis in mice tissues were accordingly detected by Immunohistochemistry and TUNEL.ResultsHigh expression of TRIP13 in HCC affected the survival rate and it was enriched in RNA degradation and fatty acid metabolism according to bioinformatics and prediction from previous literature. Increased expression of TRIP13 in HCC patient tissues was associated with the progression of HCC. Silencing TRIP13 inhibited cell viability, migration and invasion, and induced cell apoptosis. TRIP13 knockdown also suppressed the formation of tumor in vivo. Meanwhile, silencing TRIP13 decreased the expressions of Ki67 and MMP-2 and increased the expressions of TIMP-2, active-caspase-3 and TGF-β1/smad3 signaling- related genes.ConclusionsSilencing TRIP13 acts as a tumor suppresser of HCC to repress cell growth and metastasis in vitro and in vivo, and such a phenomenon possibly involved activation of TGF-β1/smad3 signaling.

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Elevated Expression of Thyroid Hormone Receptor-Interacting Protein 13 Drives Tumorigenesis and Affects Clinical Outcome

Abstract: TRIP13 is highly expressed in multiple tumors and may be used as a potential prognostic marker and therapeutic target.

Cited by 25 publications

References 26 publications

Elevated TRIP13 drives the AKT/mTOR pathway to induce the progression of hepatocellular carcinoma via interacting with ACTN4

Elevated TRIP13 drives the AKT/mTOR pathway to induce the progression of hepatocellular carcinoma via interacting with ACTN4

LncRNA TINCR is associated with clinical progression and serves as tumor suppressive role in prostate cancer

Silencing TRIP13 inhibits cell growth and metastasis of hepatocellular carcinoma by activating of TGF-β1/smad3

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