Ribonuclease H2 Subunit A impacts invasiveness and chemoresistance resulting in poor survivability of breast cancer in ER dependent manner.

Ribonuclease H2 Subunit A impacts invasiveness and chemoresistance resulting in poor survivability of breast cancer in ER dependent manner. Am J Transl Res. 2020;12(5):2281-2294 Authors: Shen J, Lin S, Liu L, Wang C Abstract Ribonuclease H2 subunit A (RNASEH2A), a member of the RNase HII family, acts in DNA replication by mediating removal of lagging-strand Okazaki fragment RNA primers. We explored the roles of RNASEH2A in the prognosis of breast cancer, specifically in relation to proliferation, invasiveness, and sensitivity to cytotoxins of cells in the estrogen receptor (ER)-positive MCF-7 and the ER-negative MDA-MB-231 breast cancer cell lines. We collected 26 datasets from around the world, comprising 7815 accessible cases. In these datasets, we probed the association between expression of RNASEH2A and clinical parameters, primarily by inhibiting the expression of RNASEH2A with siRNAs. Such inhibition inhibited the growth and invasiveness of MCF-7 cells. Independent and pooled Kaplan-Meier and Cox analyses revealed that RNASEH2A overexpression was associated with aggressiveness and poor outcomes in a dose-dependent manner in breast cancers of ER-positive subtypes, but not with ER-negative subtypes. The prognostic performance of RNASEH2A mRNA in ER-positive breast cancer was comparable to that for other gene signatures, such as the 21-gene recurrence score. Overexpression of RNASEH2A was also positively associated with cancer cell resistance to chemot...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research

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Breast Cancer. 2021 Sep 25. doi: 10.1007/s12282-021-01299-w. Online ahead of print.NO ABSTRACTPMID:34562259 | DOI:10.1007/s12282-021-01299-w
Source: Breast Cancer - Category: Cancer & Oncology Authors: Source Type: research
September 8, 2021 (RARITAN, N.J.) – The Janssen Pharmaceutical Companies of Johnson &Johnson announced today that more than ten data presentations from its lung cancer, bladder cancer and prostate cancer portfolio and pipeline will be featured during the European Society for Medical Oncology (ESMO) Annual Congress 2021 virtual meeting, September 16–21. Further details about these data and the science Janssen is advancing will be made available throughout ESMO via the Janssen Oncology Virtual Newsroom.“With a diverse oncology portfolio and pipeline spanning bladder cancer, lung cancer and prostate canc...
Source: Johnson and Johnson - Category: Pharmaceuticals Tags: Innovation Source Type: news
CONCLUSION: This study presents a distinct genetic architecture in luminal-A breast cancer potentially responsible for differential response to chemotherapy. Further studies on large cohorts of breast cancer patients are suggested for implementation in personalized medicine.PMID:34495459 | DOI:10.1007/s11033-021-06681-7
Source: Mol Biol Cell - Category: Molecular Biology Authors: Source Type: research
ciej Zylicz Analyzing the TCGA breast cancer database, we discovered that patients with the HER2 cancer subtype and overexpression of MDM2 exhibited decreased post-treatment survival. Inhibition of MDM2 expression in the SKBR3 cell line (HER2 subtype) diminished the survival of cancer cells treated with doxorubicin, etoposide, and camptothecin. Moreover, we demonstrated that inhibition of MDM2 expression diminished DNA repair by homologous recombination (HR) and sensitized SKBR3 cells to a PARP inhibitor, olaparib. In H1299 (TP53−/−) cells treated with neocarzinostatin (NCS), overexpression of MDM2 WT or E3...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
CONCLUSION: We report for the first time the prevalence of gBRCA and HRR mutations in an Asian cohort of patients with HER2-negative MBC. Our results suggest that BRCA mutation testing is valuable to determine appropriate treatment options for patients with hormone receptor-positive or triple-negative MBC.STUDY REGISTRATION: NCT03078036.PMID:34467476 | DOI:10.1007/s12282-021-01283-4
Source: Breast Cancer - Category: Cancer & Oncology Authors: Source Type: research
Triple-negative breast cancer (TNBC) is a clinically aggressive disease with abundant variants that cause homologous recombination repair deficiency (HRD). Whether TNBC patients with HRD are sensitive to anthr...
Source: BMC Medicine - Category: Internal Medicine Authors: Tags: Research article Source Type: research
Triple negative breast cancer (TNBC), accounts for approximately 15% of early-stage breast cancer diagnoses and is characterized by a younger age at diagnosis and more aggressive features such as more advanced stage and worse survival [1,2]. TNBC is a heterogeneous disease, which can include chemoresistant cases which are associated with early relapse and adverse outcomes and a contrasting group of chemosensitive tumors which with multimodality therapy can have a very low risk of relapse [3]. Pre-clinical data suggest that TNBC are associated with dysfunctional DNA-repair mechanisms (e.g.
Source: Cancer Treatment Reviews - Category: Cancer & Oncology Authors: Source Type: research
Oncologist. 2021 Jul 26. doi: 10.1002/onco.13912. Online ahead of print.ABSTRACTFamilial pancreatic adenocarcinoma (PDAC) is most commonly related to inheritance of a pathogenic BRCA variant (1). The National Comprehensive Cancer Network (NCCN) recommends germline testing for patients diagnosed with PDAC and recommends platinum-based chemotherapy as the preferred initial systemic therapy for patients harboring a pathogenic BRCA germline variant with PDAC. (2) PDACs related to pathogenic BRCA germline variants typically demonstrate BRCA loss of heterozygosity (LOH) which results in ineffective DNA damage repair due to a lac...
Source: The Oncologist - Category: Cancer & Oncology Authors: Source Type: research
Expert Opin Pharmacother. 2021 Jul 26:1-13. doi: 10.1080/14656566.2021.1952181. Online ahead of print.ABSTRACTINTRODUCTION: BRCA1 and BRCA2 (BRCA1/2) mutation breast cancers constitute an uncommon, but unique group of breast cancers that present at a younger age, and are underscored by genomic instability and accumulation of DNA damage. Talazoparib is a potent poly(ADP-ribose) polymerase (PARP) inhibitor that exploits impaired DNA damage response mechanisms in this population of patients and results in significant efficacy. Based on the results of the EMBRACA trial, talazoparib was approved for the treatment of patients wi...
Source: Expert Opinion on Pharmacotherapy - Category: Drugs & Pharmacology Authors: Source Type: research
Oncologist. 2021 Jul 26. doi: 10.1002/onco.13912. Online ahead of print.ABSTRACTFamilial pancreatic adenocarcinoma (PDAC) is most commonly related to inheritance of a pathogenic BRCA variant (1). The National Comprehensive Cancer Network (NCCN) recommends germline testing for patients diagnosed with PDAC and recommends platinum-based chemotherapy as the preferred initial systemic therapy for patients harboring a pathogenic BRCA germline variant with PDAC. (2) PDACs related to pathogenic BRCA germline variants typically demonstrate BRCA loss of heterozygosity (LOH) which results in ineffective DNA damage repair due to a lac...
Source: The Oncologist - Category: Cancer & Oncology Authors: Source Type: research
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