Dataset Information

Role of lamin A in regulation of DNA Damage Response pathways in ovarian cancer

ABSTRACT: A-type lamins, the key structural components of the nucleus, are emerging as regulators in the maintenance of nuclear architecture and genome organization. Extensive research for the last two decades has enormously contributed in understanding the roles of lamins in various signaling mechanisms which frequently go awry in neoplasias. It is interesting to know that alteration in lamin A/C expression and distribution drives tumorigenesis thus modifying its expression can be a potent therapeutic approach. One of the important signatures of a cancer cell is its inability to repair DNA damage which befalls due to a number of genomic defects that transform the cells to be sensitive to chemotherapeutic agents. Also, the errors in DNA repair mechanism are accompanied by high replication rate. This genomic and chromosomal instability is the most conventional feature found in cases of high grade ovarian serous carcinoma. Here, we report elevated levels of lamins in OVCAR3 cells (High grade ovarian serous carcinoma cell line) with respect to IOSE (Immortalised ovarian surface epithelial cells) and the altered damage repair machineries in both the cell lines. We have analysed the changes in global gene expression in sequel to DNA damage induced by etoposide in lamin A upregulated ovarian carcinoma background and reported a number of differentially expressed genes associated with pathways conferring cellular proliferation and chemoresistance. We highlight new avenues unravelling the role of an upregulated lamin A in confronting chemically induced genomic instability in the context of ovarian cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE211529 | GEO | 2022/08/23

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Low-grade serous ovarian carcinoma is believed to arise from serous borderline ovarian tumors, yet the progression from serous borderline tumors to low-grade serous ovarian carcinoma remains poorly understood. The purpose of this study was to identify differentially expressed genes between the two groups. Expression profiles were generated from 6 human ovarian surface epithelia (HOSE), 8 serous borderline ovarian tumors (SBOT), 13 low-grade serous ovarian carcinomas (LG), and 22 high-grade serous ovarian carcinomas (HG). The anterior gradient homolog 3 (AGR3) gene was found to be highly upregulated in serous borderline ovarian tumors; this finding was validated by real-time quantitative RT-PCR, Western blotting, and immunohistochemistry. Anti-AGR3 immunohistochemistry was performed on an additional 56 LG and 103 HG tissues and the results were correlated with clinical data. Expression profiling determined that 1254 genes were differentially expressed (P < 0.005) between SBOT, LG and HG tumors. Serous borderline ovarian tumors exhibited robust positive staining for AGR3, with a lower percentage of tumor cells stained in LG and HG. Immunofluorescence staining indicated that AGR3 expression was limited to ciliated cells. Tumor samples with a high percentage (>10%) of AGR3 positively stained tumor cells were associated with improved longer median survival in both the LG (P = 0.013) and HG (P = 0.008) serous ovarian carcinoma groups. The progression of serous borderline ovarian tumors to low-grade serous ovarian carcinoma may involve the de-differentiation of ciliated cells. AGR3 could serve as a prognostic marker for survival in patients with low-grade and high-grade serous ovarian carcinomas. Total RNA were extracted from microdissected human ovarian surface epithelia (HOSE, n=6), and microdissected serous borderline ovarian tumors (LMP, n=8), low-grade serous ovarian carcinomas (LGOSC, n=13), and 22 high-grade serous ovarian carcinomas (HGOSC, n=22). Gene Expression profiles were then generated with commercial GeneChip Human Genome U133 Plus 2.0 Array. dChip was used to identify significant differentially expressed genes between LMP/LGOSC and HGOSC

Dataset Information

Role of lamin A in regulation of DNA Damage Response pathways in ovarian cancer

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets