TCP10L acts as a tumor suppressor by inhibiting cell proliferation in hepatocellular carcinoma

Zuo, Jie; Cai, Hao; Wu, Yanhua; Ma, Hongshen; Jiang, Wei; Liu, Chao; Han, Dingding; Ji, Guangchen; Liu, Yu

doi:10.1016/j.bbrc.2014.02.049

Cited by 4 publications

(4 citation statements)

References 22 publications

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“…It is therefore of great interest to identify whether TCP10L affects the ubiquitination of MAD1 in future studies. Previously, we have reported a down-regulated expression pattern of TCP10L in human HCC specimens (9) . Together, these data lead to a hypothesis that during cancer progression down-regulated TCP10L results in MAD1 protein being more easily degraded by the proteasome, which then facilitates MYC-mediated cancer progression.…”

Section: Discussionmentioning

confidence: 91%

“…TCP10L contains a putative leucine zipper (LZ) domain, which is required for its homo-dimerization but not for its nuclear localization (8) . Recently, our lab reported that TCP10L was a potential tumor suppressor in hepatocellular carcinoma (HCC) (9) . In this study, we aim to further explore the molecular mechanism accounting for TCP10L’s function in HCC cells.…”

Section: Introductionmentioning

confidence: 99%

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TCP10L synergizes with MAD1 in transcriptional suppression and cell cycle arrest through mutual interaction

et al. 2016

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T-complex protein 10A homolog 2 (TCP10L) was previously demonstrated to be a potential tumor suppressor in human hepatocellular carcinoma (HCC). However, little is known about the molecular mechanism. MAX dimerization protein 1 (MAD1) is a key transcription suppressor that is involved in regulating cell cycle progression and Myc-mediated cell transformation. In this study, we identified MAD1 as a novel TCP10L-interacting protein. The interaction depends on the leucine zipper domain of both TCP10L and MAD1. TCP10L, but not the interaction-deficient TCP10L mutant, synergizes with MAD1 in transcriptional repression, cell cycle G1 arrest and cell growth suppression. Mechanistic exploration further revealed that TCP10L is able to stabilize intracellular MAD1 protein level. Consistently, the MAD1-interaction-deficient TCP10L mutant exerts no effect on stabilizing the MAD1 protein. Taken together, our results strongly indicate that TCP10L stabilizes MAD1 protein level through direct interaction, and they cooperatively regulate cell cycle progression. [BMB Reports 2016; 49(6): 325-330]

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

TCP10L synergizes with MAD1 in transcriptional suppression and cell cycle arrest through mutual interaction

et al. 2016

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“…Previously, we found that the TCP10L expression level is downregulated in HCC (20). To understand the clinical significance of this finding, we further analyzed the relationship between the expression level of TCP10L mRNA and clinical pathological features of HCC.…”

Section: Tcp10l Expression Is Negatively Associated With Afp Levelmentioning

confidence: 97%

“…TCP10L contains a putative leucine zipper (LZ) domain, which is required for homodimerization and heterodimeriza-tion with other LZ-containing proteins ( 16 - 19 ). Recently, we reported that TCP10L is a potential tumor suppressor in HCC ( 20 ). TCP10L stabilizes the MAD1 protein level through direct interaction, and they cooperatively regulate cell cycle progres-sion ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

TCP10L negatively regulates alpha-fetoprotein expression in hepatocellular carcinoma

et al. 2020

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Alpha-fetoprotein (AFP) is one of the most commonly used and reliable biomarkers for Hepatocellular carcinoma(HCC). However, the underlying mechanism of AFP expression in HCC is poorly understood. In this study, we found that TCP10L, a gene specifically expressed in the liver, is down-regulated in HCC and that its expression inversely correlates with AFP expression. Moreover, overexpression of TCP10L suppresses AFP expression whereas knockdown of TCP10L increases AFP expression, suggesting that TCP10L might be a negative regulator of AFP. We found that TCP10L is associated with the AFP promoter and inhibits AFP promoter-driven transcriptional activity. Taken together, these results indicate that TCP10L negatively regulates AFP expression in HCC and that it could be a potential prognostic marker and therapeutic target for HCC.

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Frameshift Mutations in Repeat Sequences of ANK3, HACD4, TCP10L, TP53BP1, MFN1, LCMT2, RNMT, TRMT6, METTL8 and METTL16 Genes in Colon Cancers

Yeon

Choi

et al. 2017

Pathol. Oncol. Res.

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Diminished ANK3 contributes to cell survival by inhibiting detachment-induced apoptosis. TP53BP1 that interacts with p53 and MFN1 that encodes a mitochondrial membrane protein are considered to have tumor suppressor gene (TSG) functions. HACD4 involving fatty acid synthesis and TCPL10 with transcription regulation functions are considered TSGs. Many genes involved in DNA methylations such as LCMT2, RNMT, TRMT6, METTL8 and METTL16 are often perturbed in cancer. The aim of our study was to find whether these genes were mutated in colorectal cancer (CRC). In a genome database, we observed that each of these genes harbored mononucleotide repeats in the coding sequences, which could be mutated in cancers with high microsatellite instability (MSI-H). For this, we studied 124 CRCs for the frameshift mutations of these genes and their intratumoral heterogeneity (ITH). ANK3, HACD4, TCP10L, TP53BP1, MFN1, LCMT2, RNMT, TRMT6, METTL8 and METTL16 harbored 11 (13.9%), 3 (3.8%), 0 (0%), 5 (6.3%), 1 (1.3%), 2 (2.5%), 4 (5.1%), 3 (3.8%), 2 (2.5%) and 2 (2.5%) of 79 CRCs with MSI-H, respectively. However, we found no such mutations in microsatellite stable (MSS) cancers in the nucleotide repeats. There were ITH of the frameshift mutations of ANK3, MFN1 and TP53BP1 in 1 (6.3%), 1 (6.3%) and 1 (6.3%) cases, respectively. Our data exhibit that cancer-related genes ANK3, HACD4, TP53BP1, MFN1, LCMT2, RNMT, TRMT6, METTL8 and METTL16 harbor mutational ITH as well as the frameshift mutations in CRC with MSI-H. Also, the results suggest that frameshift mutations of these genes might play a role in tumorigenesis through their inactivation in CRC.

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TCP10L acts as a tumor suppressor by inhibiting cell proliferation in hepatocellular carcinoma

Cited by 4 publications

References 22 publications

TCP10L synergizes with MAD1 in transcriptional suppression and cell cycle arrest through mutual interaction

TCP10L synergizes with MAD1 in transcriptional suppression and cell cycle arrest through mutual interaction

TCP10L negatively regulates alpha-fetoprotein expression in hepatocellular carcinoma

Frameshift Mutations in Repeat Sequences of ANK3, HACD4, TCP10L, TP53BP1, MFN1, LCMT2, RNMT, TRMT6, METTL8 and METTL16 Genes in Colon Cancers

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