POLQ-like helicase (HELQ), an evolutionarily conserved 3'-5' DNA helicase, is markedly overexpressed in platinum-resistant ovarian cancer (OC), which is correlated with a poor prognosis. However, the mechanisms linking HELQ with resistance to platinum-based chemotherapy remain unkonwn. Our study presents both in vitro and in vivo evidence that elevated HELQ expression is linked to increased chemoresistance in OC models, with reduced HELQ levels enhancing their sensitivity to platinum agents. The expression of γH2AX, RPA1 and 53BP1 determined by immunofluorescence and western blot indicated that HELQ could promote platinum-induced DNA damage repair. HELQ was found to promote OC platinum resistance by regulating the expression of poly (ADP-ribose) polymerase 1(PARP1), which could be reversed by PARP1 downregulation. Furthermore, in vitro experiments showed that HELQ overexpression sensitizes OC cells to PARP inhibitors (PARPi). Immunohistochemical analysis indicates that diminished HELQ expression in tumor tissues correlates with disease progression in patients with first-line maintenance therapy with PARPi, whereby higher expression levels predict improved progression-free survival. Notably, we found a positive correlation between PARP1 and HELQ expression. In conclusion, HELQupregulats PARP1 to promote platinum resistance in OC and warrants consideration as an emerging biomarker for monitoring therapeutic responses to chemotherapy and PARPi treatment in ovarian cancer.

Lung cancer has the highest fatality rate among malignant tumors in the world. Finding new biomarkers of drug resistance is of great importance in the prognosis of lung cancer patients. We found that the polymorphisms of Adenylate Cyclase 1 (ADCY1) are significantly associated with platinum-based chemotherapy resistance in lung cancer patients in our previous research. In this study, we wanted to identify the mechanism of ADCY1 affecting platinum resistance. We used an MTT assay to find if the expression of ADCY1 is associated with the sensitivity of cisplatin in A549, H1299, and A549-DDP cells. Then, we performed CCK-8 tests to detect the absorbance of these cells stimulated by ADCY1, which can discover the cell proliferation that is affected by ADCY1. We investigated cell apoptosis and cell cycles regulated by ADCY1 through the flow cytometry assay. RNA sequencing was used to find the downstream genes affected by ADCY1 which may be associated with drug resistance in lung cancer patients. ADCY1 has higher expression in lung cancer cells than in normal cells. ADCY1 can affect cisplatin resistance in lung cancer cells by regulating cell proliferation, cell apoptosis, and the cell cycle. It may control cell apoptosis by regulating the classical apoptosis biomarkers Bax and Bcl2. Our study showed that ADCY1 may be a new biomarker in the prognosis of lung cancer patients. Much work remains to be carried out to clarify the mechanism in this important emerging field.