جستجوی مقالات مرتبط با کلیدواژه "nhej" در نشریات گروه "پزشکی"

 Hypoxia-inducible factor 1α (HIF1α), a key transcription factor activated during low oxygen levels, influences cell cycle and metastasis. Hypoxia induces double-strand breaks (DSBs), a highly carcinogenic process.

 This study aimed to elucidate the impact of HIF1α down-regulation on the expression of XRCC4 and XRCC7, key components of the non-homologous end joining (NHEJ) pathway crucial for DSB repair.

 HeLa and [human embryonic kidney (HEK)293] cells underwent culture, transfection with HIF1α small interfering ribonucleic acid (siRNA), and viability assessment after 48 hours. Subsequent examination included cell cycle alterations. Ribonucleic acid extraction, complementary deoxyribonucleic acid (cDNA) synthesis, and RT-qPCR were performed to compare the fold-change in HIF1α, XRCC4, and XRCC7 gene expression, followed by statistical analyses.

 Downregulating HIF1α using siRNA resulted in reduced viability and increased apoptosis in both HeLa and HEK293 cells 48 hours after transfection. The findings also indicated a significant decrease in XRCC4 expression; nevertheless, XRCC7 expression remained unchanged in both cell lines.

 This study underscores that HIF1α potentially modulates the NHEJ pathway through XRCC4, presenting itself as a plausible target for cancer therapy.

Radiotherapy is an effective and important therapeutic method for breast cancer, but at the same time it has a radiation-induced bystander effect on normal tissue around the tumor. Repair of double-strand breaks (DSBs) by normal cells can reduce the extent of damage caused by this effect. Caveolin-1 (Cav-1) is an important regulatory molecule in cell signal transduction. However, the response of normal human mammary epithelial cells following low dose radiation (LDR)- induced DSBs and the role of Cav-1 in the repair of the DSBs are not clear. The present study examined the DNA damage repair mechanism triggered by LDR in human mammary epithelial cells.
Human mammary epithelial (MCF10A) and Cav-1 haplo-insufficiency (MCF10A-ST1) cells were irradiated with LDR gamma rays and the effect of this radiation on cell proliferation was determined by cytometric method. Western blot analysis was then used to measure the expression levels of different proteins associated with cell proliferation and DNA repair.
LDR enhanced the radiation responsiveness of MCF10A cells in a dose- and time-dependent manner. At a dose of 100 cGy, LDR increased the expression levels of several proteins involved in DNA repair pathways, such as ATM, p53, DNA-PKcs and also activated Cav-1-mediated cell proliferation and survival pathways, such as the MAPK and AKT pathways. The expression of the various DNA repair related proteins was changed after down-regulating the Cav-1 expression.
LDR could increase the radiation responsiveness of human mammary epithelial cells through activating the DNA repair pathways, including both HR and NHEJ pathways, as well as triggering the cell proliferation and survival pathways, both of which required Cav-1.