Elevated Levels of Lamin A Promote HR and NHEJ-Mediated Repair Mechanisms in High-Grade Ovarian Serous Carcinoma Cell Line

Extensive research for the last two decades has significantly contributed to understanding the roles of lamins in the maintenance of nuclear architecture and genome organization which is drastically modified in neoplasia. It must be emphasized that alteration in lamin A/C expression and distribution is a consistent event during tumorigenesis of almost all tissues of human bodies. One of the important signatures of a cancer cell is its inability to repair DNA damage which befalls several genomic events that transform the cells to be sensitive to chemotherapeutic agents. This genomic and chromosomal instability is the most common 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) in comparison to IOSE (immortalised ovarian surface epithelial cells) and, consequently, altered damage repair machinery in OVCAR3. We have analysed the changes in global gene expression as a sequel to DNA damage induced by etoposide in ovarian carcinoma where lamin A is particularly elevated in expression and reported some differentially expressed genes associated with pathways conferring cellular proliferation and chemoresistance. We hereby establish the role of elevated lamin A in neoplastic transformation in the context of high-grade ovarian serous cancer through a combination of HR and NHEJ mechanisms.

Automated summary

Extensive research in the past twenty years has greatly contributed to our understanding of the roles of lamins in maintaining nuclear architecture and genome organization, which are significantly altered in cancer formation. Alterations in the expression and distribution of lamin A/C have been consistently observed in the development of almost all types of human tumors. One characteristic of cancer cells is their inability to repair DNA damage, leading to genomic instability and increased sensitivity to chemotherapy. In this study, we found elevated levels of lamins in OVCAR3 cells, a high-grade ovarian serous carcinoma cell line, as well as altered DNA damage repair machinery. Furthermore, we identified differentially expressed genes associated with cellular proliferation and chemoresistance in ovarian carcinoma induced by etoposide, with lamin A showing particularly elevated expression. Our findings suggest that elevated lamin A plays a role in neoplastic transformation in high-grade ovarian serous cancer through a combination of HR and NHEJ mechanisms.