Expression analysis of the MCPH1/BRIT1 and BRCA1 tumor suppressor genes and telomerase splice variants in epithelial ovarian cancer

Alsiary, Rawiah; Brownhill, Samantha; Brüning-Richardson, Anke; Hutson, Richard; Griffin, Nicholas R.; Morrison, Ewan E.; Bond, Jacquelyn; Burchill, Susan A.; Bell, Sandra

doi:10.1016/j.gene.2018.05.113

Cited by 9 publications

(8 citation statements)

References 32 publications

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“…Building on this study we next examined MCPH1/BRIT1 expression in normal ovarian, endometrium and fallopian tube tissue. Strong nuclear MCPH1/BRIT1 staining was identified in ovarian epithelial cells by (90%) compared to endometrium and fallopian tube samples which are (70-80%) (27). Similarly, we identified reduced MCPH1/BRIT1 expression in 33% (84/ 252) of epithelial ovarian cancer tumour samples.…”

Section: Mcph1/brit1 In Ovarian Cancersupporting

confidence: 52%

“…Alternative splicing of the hTERT gene has been shown to impact the activity of the telomerase enzyme (hTERT) and contribute to a range of different diseases (24). Thyroid cancer, gastrointestinal carcinoma, ovarian cancer, and myelodysplastic disorders have all been linked to splice variants (25)(26)(27)(28). According to a prior study, MCPH1/BRIT1 acts as a negative regulator of the functional variant a+/b+ hTERT in ovarian cancer, while, the a-/b+ hTERT and a-/b-hTERT variants have a positive relationship with MCPH1/BRIT1 supporting its function as a potent inhibitor of telomerase activity (27).…”

Section: Telomerase Regulationmentioning

confidence: 99%

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The emerging role of MCPH1/BRIT1 in carcinogenesis

Alsolami

Aboalola²,

Malibari³

et al. 2023

Front. Oncol.

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The MCPH1 gene, also known as BRCT-repeat inhibitor of hTERT expression (BRIT1), has three BRCA1 carboxyl-terminal domains which is an important regulator of DNA repair, cell cycle checkpoints and chromosome condensation. MCPH1/BRIT1 is also known as a tumour suppressor in different types of human cancer. The expression level of the MCPH1/BRIT1 gene is decreased at the DNA, RNA or protein level in a number of types of cancers including breast cancer, lung cancer, cervical cancer, prostate cancer and ovarian cancer compared to normal tissue. This review also showed that deregulation of MCPH1/BRIT1 is significantly associated with reduced overall survival in 57% (12/21) and relapsed free survival in 33% (7/21) of cancer types especially in oesophageal squamous cell carcinoma and renal clear cell carcinoma. A common finding of this study is that the loss of MCPH1/BRIT1 gene expression plays a key role in promoting genome instability and mutations supporting its function as a tumour suppressor gene.

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Section: Mcph1/brit1 In Ovarian Cancersupporting

confidence: 52%

Section: Telomerase Regulationmentioning

confidence: 99%

The emerging role of MCPH1/BRIT1 in carcinogenesis

Alsolami

Aboalola²,

Malibari³

et al. 2023

Front. Oncol.

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“…To further understand the roles of the ten other proteins in the potential module, based on our current knowledge, we propose that EEF1A1, MDM2, CUL7, and BRCA1 are strongly related to HCC. These proteins are considered to play important roles in the pathophysiology of tumors and participate in cell growth, cell cycle regulation, and the maintenance of cell survival [58–61].…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology and Bioinformatics Approach Reveals the Therapeutic Mechanism of Action of Baicalein in Hepatocellular Carcinoma

Sun

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Liver cancer is the fourth leading cause of cancer death worldwide, and hepatocellular carcinoma (HCC) accounts for the greatest proportion of these deaths. Baicalein, a flavonoid isolated from the root of Scutellariae radix, is considered a potential candidate to treat HCC. However, the underlying molecular mechanisms remain poorly understood. In the present study, a network pharmacological approach was combined with microarray data (GSE95504) acquired from the Gene Expression Omnibus database to reveal the therapeutic mechanisms of action of baicalein at a systemic level. We identified 38 baicalein targets and 76 differently expressed genes (DEGs) following treatment with baicalein, including 55 upregulated and 21 downregulated genes. The DEGs were significantly enriched in the biological functions of apoptosis, endoplasmic reticulum stress, and PERK-mediated unfolded protein response. Protein-protein interaction (PPI) network construction and topological screening revealed a core module of PPIs including two baicalein targets, TP53 and CDK1, and two downregulated DEGs, HSPA1A and HSPA1B. Expression and survival data for these genes in the module derived from Gene Expression Profiling Interactive Analysis (GEPIA) were subjected to Kaplan–Meier analysis of overall survival and disease-free survival. Overexpression of CDK1, BRCA1, TUBB, HSPA1A, HSPA1B, and HSPA4 was associated with significantly worse overall survival, while overexpression of CDK1, CLU7, BRCA1, and TUBB was associated with significantly worse disease-free survival. These data suggest that baicalein exerts therapeutic effects against HCC via a PPI network involving TP53, CDK1, HSPA1A, and HSPA1B.

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“…Epithelial ovarian cancer (EOC) is one of the most common gynecological malignant tumors of women, exhibiting extremely high mortality, rapid metastasis, strong invasion ability, and high recurrence. [1][2][3] Due to the absence of obvious symptoms in the early stage of EOC, and the lack of specific and sensitive diagnostic methods, most patients are diagnosed at the advanced stages, and the five-year survival rate is less than 30%. 4,5 In recent years, although great strides have been made in diagnosis, surgery, chemotherapy, targeted drugs, and biological therapy, the treatment effect and prognosis of patients with advanced EOC are still terrible.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miR‐744‐5p inhibits cellular proliferation and invasion via targeting ARF1 in epithelial ovarian cancer

Zhao

Wang

Jin

et al. 2020

The Kaohsiung J of Med Scie

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miR-744-5p has been demonstrated to play an important role in cancer progression. However, the functions of miR-744-5p in epithelial ovarian cancer (EOC) are not well clarified. In this study, our aim was to investigate the role of miR-744-5p and its underlying molecular mechanism in cell progression of EOC. EOC clinical tissues and matched adjacent ovarian epithelial tissues were collected from 18 patients. Tissues and cell lines were analyzed by qPCR or Western blot to investigate the expression of miR-744-5p and ARF1 in EOC. Cell proliferative capacity was assessed by CCK8 and colony formation assays. Wound healing and transwell assays were performed to evaluate cell migration and invasion. The potential binding relation between miR-744-5p and IRF1 was demonstrated by dual luciferase report assay. The results showed that expression of miR-744-5p was low in EOC clinical tissues and cells. Overexpression of miR-744-5p inhibited proliferation, migration, and invasion of EOC cells. Further mechanistic study identified that ARF1 is a target of miR-744-5p, which is negatively correlated with the expression of miR-744-5p, and overexpression of ARF1 could reverse the inhibition of miR-744-5p on the proliferation, migration, and invasion of EOC cells. Taken together, our results indicated that miR-744-5p attenuated EOC progression via targeting IRF1, providing potential guidance for the clinical treatment of ovarian cancer.

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Expression analysis of the MCPH1/BRIT1 and BRCA1 tumor suppressor genes and telomerase splice variants in epithelial ovarian cancer

Abstract: These findings support a regulatory effect of MCPH1/BRIT1 and BRCA1 on telomerase activity, particularly the negative association between MCPH1/BRIT1 and the functional form of hTERT (α+/β+).

Cited by 9 publications

References 32 publications

The emerging role of MCPH1/BRIT1 in carcinogenesis

The emerging role of MCPH1/BRIT1 in carcinogenesis

Network Pharmacology and Bioinformatics Approach Reveals the Therapeutic Mechanism of Action of Baicalein in Hepatocellular Carcinoma

miR‐744‐5p inhibits cellular proliferation and invasion via targeting ARF1 in epithelial ovarian cancer

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