Genetic Factors in the Locoregional Management of Breast Cancer

Haffty, Bruce G.; Euhus, David M.; Pierce, Lori J.

doi:10.1200/jco.19.02859

Cited by 9 publications

(5 citation statements)

References 70 publications

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“…In addition to being genetic, cancer is also epigenetic [ 5 ]. Approximately 10% of all BC cases are related to genetics [ 6 ]. Epigenetic mechanisms play vital roles in regulating cancer progression and metastasis [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

circ_0058063 promotes breast cancer progression by upregulating DLGAP5 via sponging miR-557

Zhu

Tong

2024

CBM

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OBJECTIVE: Accumulating evidence indicates that circular RNAs (circRNAs) contribute to breast cancer (BC) development and progression. However, the role of circ_0058063 in BC and its underlying molecular processes remain unclear. METHODS: The expression of circ_0058063, miR-557, and DLGAP5 in BC tissues and cells was determined using real time quantitative PCR or western blotting. The functions of circ_0058063 in BC cells were detected using CCK-8, Transwell, caspase-3 activity, and xenograft tumor assays. The specific binding of circ_0058063/miR-557 and DLGAP5/miR-557 was verified using RNA immunoprecipitation (RIP) and dual-luciferase reporter assays. RESULTS: circ_0058063 expression was upregulated in BC tissues and cells. circ_0058063 knockdown inhibited proliferation and migration but promoted apoptosis in MCF-7 and MDA-MB-231 cells in vitro. In vivo studies further validated that the knockdown of circ_0058063 repressed tumor growth. Mechanistically, circ_0058063 directly sponged miR-557 and negatively regulated its expression. Additionally, miR-557 inhibition reversed the tumor-suppressive effects of the circ_0058063 knockdown on the survival of MDA-MB-231 and MCF-7 cells. Moreover, miR-557 directly targeted DLGAP5. DLGAP5 knockdown suppressed MCF-7 and MDA-MB-231 cell growth, and these effects were reversed by miR-557 downregulation. CONCLUSION: Our findings verify that circ_0058063 acts as a sponge for miR-557 to upregulate DLGAP5 expression. These findings suggest that the circ_0058063/miR-557/DLGAP5 axis is an important regulator of oncogenic function and may be a promising therapeutic target for BC.

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Section: Introductionmentioning

confidence: 99%

circ_0058063 promotes breast cancer progression by upregulating DLGAP5 via sponging miR-557

Zhu

Tong

2024

CBM

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“…Mutations and polymorphisms in them can lead to abnormal cell growth, which can lead to the development of cancer. Among the genes that are associated with the development and progression of breast cancer, the following are currently listed [ 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]: BRCA1 and BRCA2 genes, which have the best documented association with breast cancer; having a mutation in these genes is responsible for a 50–80% risk of breast cancer and a 45% risk of ovarian cancer before the age of 85—with a mutation in the BRCA1 gene and a 31–56% risk of breast cancer and 11–27% of ovarian cancer in BRCA2 mutation [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]; the PALB2 gene, which is responsible for the repair of damaged DNA; carriers of the defective gene have a 35% risk of developing breast cancer before the age of 70 [ 31 , 32 , 33 , 34 , 35 , 36 ]; the CHEK2 gene, which is responsible for the production of a protein that inhibits tumor growth; women with a mutation in this gene have a twice as high a risk of developing breast cancer compared to the general population [ 37 , 38 , 39 , 40 , 41 , 42 ]; the NBN gene, which encodes a protein regulating the DNA repair process and maintaining chromosome stability [ 43 , 44 , 45 , 46 , ...…”

Section: Introductionmentioning

confidence: 99%

Harnessing Epigenetics for Breast Cancer Therapy: The Role of DNA Methylation, Histone Modifications, and MicroRNA

Szczepanek

Skorupa

Jarkiewicz‐Tretyn³

et al. 2023

IJMS

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Breast cancer exhibits various epigenetic abnormalities that regulate gene expression and contribute to tumor characteristics. Epigenetic alterations play a significant role in cancer development and progression, and epigenetic-targeting drugs such as DNA methyltransferase inhibitors, histone-modifying enzymes, and mRNA regulators (such as miRNA mimics and antagomiRs) can reverse these alterations. Therefore, these epigenetic-targeting drugs are promising candidates for cancer treatment. However, there is currently no effective epi-drug monotherapy for breast cancer. Combining epigenetic drugs with conventional therapies has yielded positive outcomes and may be a promising strategy for breast cancer therapy. DNA methyltransferase inhibitors, such as azacitidine, and histone deacetylase inhibitors, such as vorinostat, have been used in combination with chemotherapy to treat breast cancer. miRNA regulators, such as miRNA mimics and antagomiRs, can alter the expression of specific genes involved in cancer development. miRNA mimics, such as miR-34, have been used to inhibit tumor growth, while antagomiRs, such as anti-miR-10b, have been used to inhibit metastasis. The development of epi-drugs that target specific epigenetic changes may lead to more effective monotherapy options in the future.

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“…Li-Fraumeni syndrome is an autosomal dominant genetic disorder resulting from the presence of a TP53 mutation. This mutation is associated with an 85% elevated risk of developing BC and a significantly increased occurrence of subsequent primary tumors within the radiation-exposed area [7,8]. Moreover, individuals harboring pathogenic germline CHEK2 mutations exhibit particularly elevated susceptibility to the onset of bilateral BC.…”

Section: Introductionmentioning

confidence: 99%

Exome Sequencing Reveals Novel Germline Variants in Breast Cancer Patients in the Southernmost Region of Thailand

Sukpan,

Sangkhathat,

Sriplung

et al. 2023

JPM

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Germline carriers of pathogenic variants in cancer susceptibility genes are at an increased risk of breast cancer (BC). We characterized germline variants in a cohort of 151 patients diagnosed with epithelial BC in the southernmost region of Thailand, where the predominant ethnicity differs from that of the rest of the country. Whole exome sequencing was used to identify and subsequently filter variants present in 26 genes known to be associated with cancer predisposition. Of the 151 individuals assessed, 23, corresponding to 15.2% of the sample, exhibited the presence of one or more pathogenic or likely pathogenic variants associated with BC susceptibility. We identified novel germline truncating variants in BRIP1, CHEK2, MSH6, PALB2, and PTEN and annotated variants of uncertain significance (VUSs), both novel and previously documented. Therefore, it is advisable to use genetic testing as an additional risk screening method for BC in this area.

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Genetic Factors in the Locoregional Management of Breast Cancer

Abstract: Author affiliations and support information (if applicable) appear at the end of this article.

Cited by 9 publications

References 70 publications

circ_0058063 promotes breast cancer progression by upregulating DLGAP5 via sponging miR-557

circ_0058063 promotes breast cancer progression by upregulating DLGAP5 via sponging miR-557

Harnessing Epigenetics for Breast Cancer Therapy: The Role of DNA Methylation, Histone Modifications, and MicroRNA

Exome Sequencing Reveals Novel Germline Variants in Breast Cancer Patients in the Southernmost Region of Thailand

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