Transmembrane and Ubiquitin-Like Domain Containing 1 Protein (TMUB1) Negatively Regulates Hepatocellular Carcinoma Proliferation via Regulating Signal Transducer and Activator of Transcription 1 (STAT1)

Chen, Yin; Fu, Hangwei; Zhang, Yida; Chen, Ping

doi:10.12659/msm.920319

Cited by 12 publications

(12 citation statements)

References 47 publications

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“…However, TMUB1 was demonstrated to be negatively correlated with HCC pathological malignancy [ 10 ] as low expression of TMUB1 correlated with poor prognosis in patients with HCC. This discrepancy may be attributed to TMUB1 playing different roles in different tissues.…”

Section: Discussionmentioning

confidence: 99%

TMUB1 Correlated with Immune Infiltration Is a Prognostic Marker for Colorectal Cancer

Hao

Huang

et al. 2022

Disease Markers

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Background. Transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1) is overexpressed in a large number of liver and esophageal tumors. However, only a few reports on the clinical significance of TMUB1 in colorectal cancer (CRC) exist. Methods. Here, we evaluated the clinical significance and potential biological role of TMUB1 using bioinformatics analysis. Univariate and multivariate analyses were performed to evaluate the relationship of TMUB1 with clinicopathological features. Gene set enrichment analysis (GSEA) was performed to identify the biological function of TMUB1, while any associations between the expression of TMUB1 and the infiltration of 24 immune cells were analyzed using simple-sample GSEA. Results. TMUB1 was significantly overexpressed in CRC tissues compared with normal controls. The high expression of TMUB1 in CRC was associated with T stage, neotype, and residual tumor. Moreover, TMUB1 was identified as an independent factor of poor disease-free survival (DFS) and short overall survival (OS). GSEA demonstrated that TMUB1 was related to hypoxia, angiogenesis, adipogenesis, inflammatory response, IL6-JAK-STAT3 signaling, apoptosis, mitotic spindle, and IL2-STAT5 signaling. The expression of TMUB1 negatively correlated with the abundance of T helper cells, Tcm cells, macrophages, and Th2 cells, whereas it positively correlated with the abundance of several immune cell types, including CD56bright and CD56dim NK cells. Conclusions. The high expression of TMUB1 is closely related to a poor prognosis in patients with CRC. TMUB1 may be a potential prognostic biomarker and be used for therapeutic approaches in CRC.

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Section: Discussionmentioning

confidence: 99%

TMUB1 Correlated with Immune Infiltration Is a Prognostic Marker for Colorectal Cancer

Hao

Huang

et al. 2022

Disease Markers

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“…Moreover, during liver regeneration, HOPS inhibits STAT3 pathways, negatively controlling hepatocyte proliferation [8]. HOPS negatively correlates with hepatocellular carcinoma malignancy, inhibiting proliferation via STAT1 signaling and promoting ubiquitination of ∆Np63 [9]. Analyzing HOPS' role in hepatocellular carcinoma proliferation, it has been shown that tumor cell growth is suppressed by controlling the ubiquitination and degradation of ∆Np63 isoforms, thus driving cells to apoptosis [10].…”

Section: Introductionmentioning

confidence: 99%

Hops/Tmub1 Heterozygous Mouse Shows Haploinsufficiency Effect in Influencing p53-Mediated Apoptosis

Ferracchiato

Di-Iacovo

Scopetti

et al. 2021

IJMS

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HOPS is a ubiquitin-like protein implicated in many aspects of cellular function including the regulation of mitotic activity, proliferation, and cellular stress responses. In this study, we focused on the complex relationship between HOPS and the tumor suppressor p53, investigating both transcriptional and non-transcriptional p53 responses. Here, we demonstrated that Hops heterozygous mice and mouse embryonic fibroblasts exhibit an impaired DNA-damage response to etoposide-induced double-strand breaks when compared to wild-type genes. Specifically, alterations in HOPS levels caused significant defects in the induction of apoptosis, including a reduction in p53 protein level and percentage of apoptotic cells. We also analyzed the effect of reduced HOPS levels on the DNA-damage response by examining the transcript profiles of p53-dependent genes, showing a suggestive deregulation of the mRNA levels for a number of p53-dependent genes. Taken together, these results show an interesting haploinsufficiency effect mediated by Hops monoallelic deletion, which appears to be enough to destabilize the p53 protein and its functions. Finally, these data indicate a novel role for Hops as a tumor-suppressor gene in DNA damage repair in mammalian cells.

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“…The activation of SCF/c-kit axis triggers cascade of MAPK pathways [ 21 ], of which the ERK pathway is generally responsible for cell differentiation and proliferation, whereas the JNK pathway is involved in apoptosis [ 22 ]. Additionally, the phospho-ERK translocation from the cytoplasm to the nucleus stimulates the activity of transcription factors such as STAT1/3, Pax6, and CREB [ 23 – 25 ]. In addition, CBP expression is markedly increased in breast cancer cells treated with cancer-associated adipose tissue [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

MAPK/ERK-CBP-RFPL-3 Mediates Adipose-Derived Stem Cell-Induced Tumor Growth in Breast Cancer Cells by Activating Telomerase Reverse Transcriptase Expression

Qian

et al. 2022

Stem Cells International

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Adipose-derived stem cells (ASCs) improve the self-renewal and survival of fat grafts in breast reconstruction after oncology surgery. However, ASCs have also been found to enhance breast cancer growth, and its role in tumor proliferation remains largely elusive. Here, we explored a novel mechanism that mediates hTERT reactivation during ASC-induced tumor growth in breast cancer cells. In this study, we found the proliferative ability of breast cancer cells markedly increased with ASC coculture. To explore the molecular mechanism, we treated cells with anibody/inhibitor and found that the activation of MEK-ERK pathway was triggered in breast cancer cells by SCF secreted from ASCs, leading to the nuclear recruitment of CBP. As a coactivator of hTERT, CBP subsequently coordinated with RFPL-3 upregulated hTERT transcription and telomerase activity. The inhibition of CBP and RFPL-3 abrogated the activation of hTERT transcription and the promotion of proliferation in breast cancer cells with cocultured ASCs in vitro and in vivo. Collectively, our study findings indicated that CBP coordination with RFPL-3 promotes ASC-induced breast cancer cell proliferation by anchoring to the hTERT promoter and upregulating telomerase activity, which is activated by the MAPK/ERK pathway.

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Transmembrane and Ubiquitin-Like Domain Containing 1 Protein (TMUB1) Negatively Regulates Hepatocellular Carcinoma Proliferation via Regulating Signal Transducer and Activator of Transcription 1 (STAT1)

Cited by 12 publications

References 47 publications

TMUB1 Correlated with Immune Infiltration Is a Prognostic Marker for Colorectal Cancer

TMUB1 Correlated with Immune Infiltration Is a Prognostic Marker for Colorectal Cancer

Hops/Tmub1 Heterozygous Mouse Shows Haploinsufficiency Effect in Influencing p53-Mediated Apoptosis

MAPK/ERK-CBP-RFPL-3 Mediates Adipose-Derived Stem Cell-Induced Tumor Growth in Breast Cancer Cells by Activating Telomerase Reverse Transcriptase Expression

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