Actin Gamma 1, a new skin cancer pathogenic gene, identified by the biological feature‐based classification

Dong, Xiaorong; Han, Yingsheng; Sun, Zhenliang; Xu, Jianguang

doi:10.1002/jcb.26301

Cited by 31 publications

(23 citation statements)

References 57 publications

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“…ACTG1 is essential for the stability of hair cell stereocilia,25 while its mutations may cause deafness or the Baraitser–Winter syndrome 26. A recent study revealed the oncogenic effect of ACTG1 in skin cancer, wherein its overexpression may lead to cancer cell proliferation and migration 27. However, the role of ACTG1 in HCC has not been previously reported.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, RRAD was found to play a critical role in the negative regulation of glycolysis through the induction of actin gamma 1 (ACTG1), which belongs to γ-actins, a class of proteins existing in most cell types as components of the cytoskeleton. ACTG1 is reportedly related to conditions such as hearing loss,11 while a more recent study implicated that ACTG1 overexpression could improve the proliferation and clone formation of skin cancer cells 12. However, the biological functions of ACTG1 in HCC cells have not been studied yet.…”

Section: Introductionmentioning

confidence: 99%

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<p>RRAD suppresses the Warburg effect by downregulating ACTG1 in hepatocellular carcinoma</p>

Yan¹,

Xu²,

Zhang³

et al. 2019

OTT

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Purpose Hepatocellular carcinoma (HCC) is a common malignancy with poor prognosis and limited therapeutic options. Ras-related associated with diabetes (RRAD) belongs to the subfamily of Ras-related GTPases and is associated with several types of cancer, including HCC, although the mechanisms involving RRAD in HCC remains unknown. Patients and methods We aimed to elucidate the role of RRAD and whether it affects glucose metabolism in HCC by immunohistochemically examining tissue samples from HCC patients and assessing the effect of RRAD overexpression and knockdown on the glucose metabolism, proliferation, cell cycle, and apoptosis of HCC cell lines SK-Hep-1 and Huh7, as well as on tumor progression in vivo. Results We demonstrated that RRAD binds to actin gamma 1 (ACTG1). RRAD suppressed aerobic glycolysis in HCC by downregulating ACTG1. On the other hand, ACTG1 promoted HCC proliferation by regulating the cell cycle via downregulation of cyclins and cyclin-dependent kinases and inhibited apoptosis through the mitochondrial apoptosis pathway in vitro. In addition, RRAD retarded tumor growth by downregulating ACTG1 in vivo. ACTG1 was overexpressed in HCC tissues compared with adjacent normal tissues, whereas the expression of RRAD was low in tumor tissues. Low RRAD levels were significantly correlated with large tumor size and advanced tumor stage; high ACTG1 levels were significantly correlated with advanced tumor stage. Furthermore, Kaplan–Meier survival curves showed that HCC patients with high RRAD and low ACTG1 expression may have a better prognosis. Conclusion We have shown that RRAD exhibits a tumor-suppressing role in HCC by downregulating glucose metabolism and ACTG1 expression, thus lowering cell proliferation, arresting the cell cycle, and increasing apoptosis. These findings indicate that ACTG1 may act as a downstream effector of RRAD and open a new avenue for potential HCC treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

<p>RRAD suppresses the Warburg effect by downregulating ACTG1 in hepatocellular carcinoma</p>

Yan¹,

Xu²,

Zhang³

et al. 2019

OTT

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“…27,28 The proteins involved in cell migration are essential for the rearrangements among cytoskeletal networks that are needed, and they play a critical role in various diseases. 29 It has been hypothesized that ACTG1 regulates cell migration and proliferation via the ROCK signaling pathway 14 and that it has an important role in lung cancer metastasis. 30 Furthermore, it has been reported that gamma-actin regulates the cell migration of SH-EP neuroblastoma cells, 31 affects cancer cell motility and influences the invasiveness of human colon cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, ACTG1 has been found to be highly expressed in acute lymphoblastic leukemia, osteosarcoma, and skin cancer, thereby indicating that it may play a role in the development and progression of cancer. 9,13,14 Despite these insights, however, the clinical significance of ACTG1 in ovarian cancer remains unclear. Therefore, the goals of this study were to obtain a profile of ACTG1 expression in ovarian cancer tissue and to investigate its association with clinicopathological parameters in order to analyze its role in the development of ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

Reduced levels of actin gamma 1 predict poor prognosis in ovarian cancer patients

Chen

Wang

Yuan

et al. 2020

J of Obstet and Gynaecol

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Aim To investigate the expression and function of actin gamma 1 (ACTG1) in ovarian cancer. Methods We performed immunohistochemical staining of 176 ovarian cancer tissue samples in a human tissue microarray to detect expression of ACTG1. Staining intensity was examined in relation to clinicopathological parameters. To investigate the prognostic value of ACTG1, ACTG1 mRNA data from 300 ovarian cancer patients in The Cancer Genome Atlas database were examined. Results The immunohistochemical results demonstrated that levels of ACTG1 were reduced in the samples of human ovarian cancer tissue that were examined, and the levels negatively correlated with various clinicopathological parameters. Levels of ACTG1 mRNA also negatively correlated with clinical stage. In Kaplan–Meier survival analysis, higher levels of ACTG1 mRNA were associated with improved overall survival. In multivariate analysis by Cox regression, ACTG1 expression was identified as an independent prognostic marker of favorable overall survival. Conclusion ACTG1 may represent a valuable marker for the prognosis of ovarian cancer, and further studies of ACTG1 are warranted.

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“…Studies have demonstrated that miR-888 may reduce the mRNA expression levels of all four adherens junction pathway-associated genes, including E-cadherin, ACTG1, receptor-type tyrosine-protein phosphatase T and cell division cycle 42 in MCF-7 cells (24). Additionally, ACTG1 has been reported to exhibit high expression levels in skin cancer tissue, where it may regulate A431 cell proliferation and migration via the Rho-associated protein kinase signaling pathway (25). ACTG1 has also been predicted to be a target gene of miR-145-5P in non-small cell lung cancer (26).…”

Section: Discussionmentioning

confidence: 99%

ACTG1 and TLR3 are biomarkers for alcohol‑associated hepatocellular carcinoma

Gao

Tan

et al. 2018

Oncol Lett

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Alcohol consumption is a risk factor for the development of hepatocellular carcinoma (HCC); however, the association between alcohol and HCC remains unknown. The present study aimed to identify key genes related to alcohol-associated HCC to improve the current understanding of the pathology of this disease. Alcohol-associated and non-alcohol-associated HCC samples in the GSE50579 dataset of the Gene Omnibus Database were analyzed to investigate altered gene expression. Integrated bioinformatics methods were employed to clarify the biological functions of the differentially expressed genes (DEGs), including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interactions (PPIs). The present study reported that candidate biomarker micro (mi)RNAs via TargetScan Human 7.1. DEGs and their associated miRNAs (according to bioinformatics analysis) were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, 284 EGs from the GSE50579 dataset were revealed. In GO term analysis, DEGs were closely associated with the ‘regulation of nucleic acid metabolism’. KEGG pathway analysis indicated that the DEGs were tightly engaged in the ‘VEGF and VEGF receptor signaling network’, ‘proteoglycan syndecan-mediated signaling events’, ‘erbB receptor signaling’ and ‘β1 integrin cell surface interactions’. According to the results of PPI and heat map analysis, the main hub genes were centrin 3 (CETN3), Toll-like receptor 3 (TLR3), receptor tyrosine-protein kinase (ERBB4), heat shock protein family member 8, actin γ1 (ACTG1) and α-smooth muscle actin. it was demonstrated that the ACTG1, TLR3, miR-6819-3p and miRΝΑ (miR)-6877-3P had undefined associations. Furthermore, RT-qPCR analysis revealed that miR-6819-3p and miR-6877-3P may enhance the expression levels of ACTG1 and inhibit the expression levels of TLR3 in alcohol-associated HCC tissues. TLR3 and ACTG1 were proposed as potential biomarkers of alcohol-associated HCC. Investigation into the regulatory functions of miR-6819-3p and miR-6877-3P may provide novel insights into the treatment of alcohol-associated HCC.

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Actin Gamma 1, a new skin cancer pathogenic gene, identified by the biological feature‐based classification

Cited by 31 publications

References 57 publications

<p>RRAD suppresses the Warburg effect by downregulating ACTG1 in hepatocellular carcinoma</p>

<p>RRAD suppresses the Warburg effect by downregulating ACTG1 in hepatocellular carcinoma</p>

Reduced levels of actin gamma 1 predict poor prognosis in ovarian cancer patients

ACTG1 and TLR3 are biomarkers for alcohol‑associated hepatocellular carcinoma

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