Actin-like Protein 6A Expression Correlates with Cancer Stem Cell-like Features and Poor Prognosis in Ovarian Cancer

Chen, Po‐Ming; Wong, Chui-Na; Chu, Pei-Yi

doi:10.3390/ijms24032016

Cited by 6 publications

(7 citation statements)

References 31 publications

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“…Additionally, it has been reported to serve a role in tumorigenesis in head and neck squamous cell carcinoma (26) and glioma (25) by activating the Hippo/YAP pathway. In the context of ovarian cancer, high mRNA expression of ACTL6A has been reported to be associated with shortened OS (24) and platinum resistance (30). In the present study, public data demonstrated no significant association between ACTL6A mRNA expression and prognosis in patients with ovarian serous carcinoma; however, low ACTL6A protein expression levels, as detected by IHC, were associated with decreased OS.…”

Section: Discussioncontrasting

confidence: 59%

“…Previous studies have highlighted the amplification and upregulation of ACTL6A in numerous types of cancer, such as ovarian cancer, glioma, squamous cell carcinoma, osteosarcoma and hepatocellular carcinoma (24)(25)(26)(27)(28). ACTL6A has been implicated in promoting metastasis and epithelial-mesenchymal transition in hepatocellular carcinoma (28) and colon cancer (29).…”

Section: Discussionmentioning

confidence: 99%

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Gene amplification of chromatin remodeling factor SMARCC2 and low protein expression of ACTL6A are unfavorable factors in ovarian high‑grade serous carcinoma

Magarifuchi,

Iwasaki,

Katayama

et al. 2024

Oncol Lett

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Ovarian high-grade serous carcinoma (OHGSC) is the most common type of ovarian cancer worldwide. Genome sequencing has identified mutations in chromatin remodeling factors (CRFs) in gynecological cancer, such as clear cell carcinoma, endometrioid carcinoma and endometrial serous carcinoma. However, to the best of our knowledge, the association between CRFs and OHGSC remains unexplored. The present study aimed to investigate the clinicopathological and molecular characteristics of CRF dysfunction in OHGSC. CRF alterations were analyzed through numerous methods, including the analysis of public next-generation sequencing (NGS) data from 585 ovarian serous carcinoma cases from The Cancer Genome Atlas (TCGA), immunohistochemistry (IHC), and DNA copy number assays, which were performed on 203 surgically resected OHGSC samples. In the public NGS dataset, the most frequent genetic alteration was actin-like protein 6A (ACTL6A) amplification at 19.5%. Switch/sucrose non-fermentable related, matrix associated, actin dependent regulator of chromatin subfamily c member 2 (SMARCC2) amplification (3.1%) was associated with significantly decreased overall survival (OS). In addition, chromodomain-helicase-DNA-binding protein 4 (CHD4) amplification (5.7%) exhibited unfavorable outcome trends, although not statistically significant. IHC revealed the protein expression loss of ARID1A (2.5%), SMARCA2 (2.5%) and SMARCA4 (3.9%). The protein expression levels of ACTL6A, SMARCC2 and CHD4 were evaluated using H-score. Patients with low protein expression levels of ACTL6A showed a significantly decreased OS. Copy number gain or gene amplification was demonstrated in ACTL6A (66.2%) and SMARCC2 (33.5%), while shallow deletion or deep deletion was demonstrated in CHD4 (70.7%). However, there was no statistically significant difference in protein levels of these CRFs, between the different copy number alterations (CNAs). Overall, OHGSC exhibited CNAs and protein loss, indicating possible gene alterations in CRFs. Moreover, there was a significant association between the protein expression levels of ACTL6A and poor prognosis. Based on these findings, it is suggested that CRFs could serve as prognostic markers for OHGSC.

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Section: Discussioncontrasting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Gene amplification of chromatin remodeling factor SMARCC2 and low protein expression of ACTL6A are unfavorable factors in ovarian high‑grade serous carcinoma

Magarifuchi,

Iwasaki,

Katayama

et al. 2024

Oncol Lett

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“…ACTL6A is an ATP-dependent SWI/SNF regulatory complex protein with chromatinremodeling components (Mani et al, 2017). Recent studies revealed that follicle-stimulating hormone (FSH)-stimulated glycolysis in ovarian malignancy comprised a higher level of the poor prognostic factor ACTL6A, which forecasted metastasis and prognosis of ovarian cancer patients (Chen et al, 2023). POLR1B, which encodes DNA-directed RNA polymerase I subunit RPA2, has been linked to Treacher Collins and may be involved in cluster headaches (Harder et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Analysis of weighted gene co-expression networks and clinical validation identify hub genes and immune cell infiltration in the endometrial cells of patients with recurrent implantation failure

Liu,

Lai,

et al. 2024

Front. Genet.

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Background:About 10% of individuals undergoing in vitro fertilization encounter recurrent implantation failure (RIF), which represents a worldwide social and economic concern. Nevertheless, the critical genes and genetic mechanisms underlying RIF are largely unknown.Methods:We first obtained three comprehensive microarray datasets “GSE58144, GSE103465 and GSE111974”. The differentially expressed genes (DEGs) evaluation, enrichment analysis, as well as efficient weighted gene co-expression network analysis (WGCNA), were employed for distinguishing RIF-linked hub genes, which were tested by RT-qPCR in our 30 independent samples. Next, we studied the topography of infiltration of 22 immune cell subpopulations and the association between hub genes and immune cells in RIF using the CIBERSORT algorithm. Finally, a novel ridge plot was utilized to exhibit the potential function of core genes.Results:The enrichment of GO/KEGG pathways reveals that Herpes simplex virus 1 infection and Salmonella infection may have an important role in RIF. After WGCNA, the intersected genes with the previous DEGs were obtained using both variance and association. Notably, the subsequent nine hub genes were finally selected: ACTL6A, BECN1, SNRPD1, POLR1B, GSK3B, PPP2CA, RBBP7, PLK4, and RFC4, based on the PPI network and three different algorithms, whose expression patterns were also verified by RT-qPCR. With in-depth analysis, we speculated that key genes mentioned above might be involved in the RIF through disturbing endometrial microflora homeostasis, impairing autophagy, and inhibiting the proliferation of endometrium. Furthermore, the current study revealed the aberrant immune infiltration patterns and emphasized that uterine NK cells (uNK) and CD4+ T cells were substantially altered in RIF endometrium. Finally, the ridge plot displayed a clear and crucial association between hub genes and other genes and key pathways.Conclusion:We first utilized WGCNA to identify the most potential nine hub genes which might be associated with RIF. Meanwhile, this study offers insights into the landscape of immune infiltration status to reveal the underlying immune pathogenesis of RIF. This may be a direction for the next study of RIF etiology. Further studies would be required to investigate the involved mechanisms.

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“…Its involvement in tumorigenesis across multiple cancers has been widely reported ( Meng et al, 2017 ). In particular, research conducted by Chen et al ( Chen et al, 2023 ) has established a correlation between ACTL6A expression and characteristics resembling those of cancer stem cells, highlighting its importance in the prognosis of ovarian cancer. Furthermore, ACTL6A has been associated with the inhibition of p21Cip1 promoter activity in epidermal squamous cell carcinoma, which contributes to the preservation of an aggressive phenotype ( Shrestha et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

ACTL6A: unraveling its prognostic impact and paving the way for targeted therapeutics in carcinogenesis

Eid,

Mamdouh,

Abdulsahib

et al. 2024

Front. Mol. Biosci.

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Introduction: Increased Actin-like 6A (ACTL6A) expression is associated with various cancers, but its comprehensive investigation across different malignancies is lacking. We aimed to analyze ACTL6A as a potential oncogene and therapeutic target using bioinformatics tools.Methods: We comprehensively analyzed ACTL6A expression profiles across human malignancies, focusing on correlations with tumor grade, stage, metastasis, and patient survival. Genetic alterations were examined, and the epigenetic landscape of ACTL6A was assessed using rigorous methods. The impact of ACTL6A on immune cell infiltration in the tumor microenvironment was evaluated, along with molecular docking studies and machine learning models.Results: Our analysis revealed elevated ACTL6A expression in various tumors, correlating with poor prognostic indicators such as tumor grade, stage, metastasis, and patient survival. Genetic mutations and epigenetic modifications were identified, along with associations with immune cell infiltration and key cellular pathways. Machine learning models demonstrated ACTL6A's potential for cancer detection.Discussion: ACTL6A emerges as a promising diagnostic and therapeutic target in cancer, with implications for prognosis and therapy. Our study provides comprehensive insights into its carcinogenic actions, highlighting its potential as both a prognostic indicator and a target for anti-cancer therapy. This integrative approach enhances our understanding of ACTL6A's role in cancer pathogenesis and treatment.

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Actin-like Protein 6A Expression Correlates with Cancer Stem Cell-like Features and Poor Prognosis in Ovarian Cancer

Cited by 6 publications

References 31 publications

Gene amplification of chromatin remodeling factor SMARCC2 and low protein expression of ACTL6A are unfavorable factors in ovarian high‑grade serous carcinoma

Gene amplification of chromatin remodeling factor SMARCC2 and low protein expression of ACTL6A are unfavorable factors in ovarian high‑grade serous carcinoma

Analysis of weighted gene co-expression networks and clinical validation identify hub genes and immune cell infiltration in the endometrial cells of patients with recurrent implantation failure

ACTL6A: unraveling its prognostic impact and paving the way for targeted therapeutics in carcinogenesis

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