Long Non-Coding RNA Neighbor of BRCA1 Gene 2: A Crucial Regulator in Cancer Biology

Long non-coding RNAs (lncRNAs) are involved in fundamental biochemical and cellular processes. The neighbor of BRCA1 gene 2 (NBR2) is a long intergenic non-coding RNA (lincRNA) whose gene locus is adjacent to the tumor suppressor gene breast cancer susceptibility gene 1 (BRCA1). In human cancers, NBR2 expression is dysregulated and correlates with clinical outcomes. Moreover, NBR2 is crucial for glucose metabolism and affects the proliferation, survival, metastasis, and therapeutic resistance in different types of cancer. Here, we review the precise molecular mechanisms underlying NBR2-induced changes in cancer. In addition, the potential application of NBR2 in the diagnosis and treatment of cancer is also discussed, as well as the challenges of exploiting NBR2 for cancer intervention.

Download Full-text

Role played by BRCA1 in regulating the cellular response to stress

Biochemical Society Transactions ◽

10.1042/bst0310257 ◽

2003 ◽

Vol 31 (1) ◽

pp. 257-262 ◽

Cited By ~ 12

Author(s):

P.M. Gilmore ◽

J.E. Quinn ◽

P.B. Mullan ◽

H.N. Andrews ◽

N. McCabe ◽

...

Keyword(s):

Cellular Response ◽

Cancer Susceptibility ◽

Susceptibility Gene ◽

Breast Cancer Susceptibility ◽

Suppressor Gene ◽

Tumour Suppressor Gene ◽

Breast Cancer Susceptibility Gene ◽

Dna Breaks ◽

Double Strand Dna Breaks ◽

Response To Stress

BRCA1 (breast-cancer susceptibility gene 1) is a tumour suppressor gene that is mutated in the germline of women with a genetic predisposition to breast and ovarian cancer. In this review, we examine the role played by BRCA1 in mediating the cellular response to stress. We review the role played by BRCA1 in detecting and signalling the presence of DNA damage, particularly double-strand DNA breaks, and look at the evidence to support a role for BRCA1 in regulating stress response pathways such as the c-Jun N-terminal kinase/stress-activated protein kinase pathway. In addition, we examine the role played by BRCA1 in mediating both cell-cycle arrest and apoptosis following different types of cellular insult, and how this may be modulated by the presence or absence of associated proteins such as p53. Finally, we explore the possibility that many of the functions associated with BRCA1 may be based on transcriptional regulation of key downstream genes that have been implicated in the regulation of these specific cellular pathways.

Download Full-text

Host Cell Reactivation and Transcriptional Activation of Carboplatin-Modified BRCA1

Breast Cancer Basic and Clinical Research ◽

10.4137/bcbcr.s14224 ◽

2014 ◽

Vol 8 ◽

pp. BCBCR.S14224 ◽

Cited By ~ 1

Author(s):

Adisorn Ratanaphan ◽

Bhutorn Canyuk

Keyword(s):

Host Cell ◽

Transcriptional Activation ◽

Cancer Susceptibility ◽

Susceptibility Gene ◽

Brca1 Gene ◽

Breast Cancer Susceptibility ◽

Breast Cancer Susceptibility Gene ◽

Cell Reactivation ◽

Host Cell Reactivation

The breast cancer susceptibility gene 1 ( BRCA1) has been shown to maintain genomic stability through multiple functions in the regulation of DNA damage repair and transcription. Its translated BRCT (BRCA1 C-terminal domain) acts as a strong transcriptional activator. BRCA1 damaged by carboplatin treatment may lead to a loss of such functions. To address the possibility of the BRCA1 gene as a therapeutic target for carboplatin, we investigated the functional consequences of the 3′-terminal region of human BRCA1 following in vitro platination with carboplatin. A reduction in cellular BRCA1 repair of carboplatin-treated plasmid DNA, using a host cell reactivation assay, was dependent on the platination levels on the reporter gene. The transcriptional transactivation activity of the drug-modified BRCA1, assessed using a one-hybrid GAL4 transcriptional assay, was inversely proportional to the carboplatin doses. The data emphasized the potential of the BRCA1 gene to be a target for carboplatin treatment.

Download Full-text

Absence of High Penetrance Genes Mutations in Familial Breast Cancer in Mizo-Mongloid Population, Northeast India

10.21203/rs.3.rs-21839/v1 ◽

2020 ◽

Author(s):

Doris Zodinpuii ◽

Bawitlung Zothankima ◽

Jeremy Lalrinsanga Pautu ◽

Doris Lallawmzuali ◽

Ashok Kumar Varma ◽

...

Keyword(s):

Breast Cancer ◽

Familial Breast Cancer ◽

Cancer Susceptibility ◽

Mutation Screening ◽

Susceptibility Gene ◽

Gene Mutations ◽

Brca1 Gene ◽

Breast Cancer Susceptibility ◽

Breast Cancer Susceptibility Gene ◽

Cancer Susceptibility Genes

Abstract Background: Breast cancer is the most prevalent cancer and leading cause of death among women globally. The present study focuses on screening germline mutations of breast cancer susceptibility genes among the unexplored Mizo breast cancers of culturally and historically homogenous population, living a unique life style habits in terms of diet and tobacco usage. Methods Mutation screening was performed using Sanger sequencing in complete coding region of BRCA1 and frequently mutated exons of TP53, PTEN, CDH1, CHEK2 and XRCC2. Several online mutation prediction tools and databases were used to check the pathogenicity of the polymorphisms observed. Results: We observed eight polymorphisms in total, in which, one variants p.P1544P in BRCA1 gene was found to be novel. No variants were found to have a potential impact on protein since all the polymorphisms are of silent substitutions. No genetic alteration was observed in the studied exons of each of TP53, PTEN, CDH1, CHEK2 and XRCC2. Conclusion: To our knowledge, the present study focusing on familial breast cancer is the first time to analyzed the prevalence of breast cancer susceptibility gene mutations using direct sequencing in Mizo population. Even though, we do not find significant amino acid change, our results suggest the need for further evaluation of broader panel genes and a challenge to screen larger sample size to establish the contribution of these gene mutations in this population.

Download Full-text