Cancer stem cells (CSCs) with enhanced tumorigenicity and chemoresistance are believed to be responsible for treatment failure and tumor relapse in ovarian cancer patients. However, it is still unclear how CSCs survive DNA-damaging agent treatment. Here, we report an elevated expression of DNA polymerase η (Pol η) in ovarian CSCs isolated from both ovarian cancer cell lines and primary tumors, indicating that CSCs may have intrinsically enhanced translesion DNA synthesis (TLS). Down-regulation of Pol η blocked cisplatin-induced CSC enrichment both in vitro and in vivo through the enhancement of cisplatin-induced apoptosis in CSCs, indicating that Pol η-mediated TLS contributes to the survival of CSCs upon cisplatin treatment. Furthermore, our data demonstrated a depletion of miR-93 in ovarian CSCs. Enforced expression of miR-93 in ovarian CSCs reduced Pol η expression and increased their sensitivity to cisplatin. Taken together, our data suggest that ovarian CSCs have intrinsically enhanced Pol η-mediated TLS, allowing CSCs to survive cisplatin treatment, leading to tumor relapse. Targeting Pol η, probably through enhancement of miR-93 expression, might be exploited as a strategy to increase the efficacy of cisplatin treatment.

Following the identification of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, we are now again facing a global highly pathogenic novel coronavirus (SARS-CoV-2) epidemic. Although the lungs are one of the most critically affected organs, several other organs, including the brain may also get infected. Here, we have highlighted that SARS-CoV-2 might infect the central nervous system (CNS) through the olfactory bulb. From the olfactory bulb, SARS-CoV-2 may target the deeper parts of the brain including the thalamus and brainstem by trans-synaptic transfer described for many other viral diseases. Following this, the virus might infect the respiratory center of brain, which could be accountable for the respiratory breakdown of COVID-19 patients. Therefore, it is important to screen the COVID-19 patients for neurological symptoms as well as possibility of the collapse of the respiratory center in the brainstem should be investigated in depth.

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Ovarian cancer is an extremely aggressive disease associated with a high percentage of tumor recurrence and chemotherapy resistance. Understanding the underlying mechanism of tumor relapse is crucial for effective therapy of ovarian cancer. DNA damage-binding protein 2 (DDB2) is a DNA repair factor mainly involved in nucleotide excision repair. Here, a novel role was identified for DDB2 in the tumorigenesis of ovarian cancer cells and the prognosis of patients with ovarian cancer. Overexpressing DDB2 in human ovarian cancer cells suppressed its capability to recapitulate tumors in athymic nude mice. Mechanistic investigation demonstrated that DDB2 is able to reduce the cancer stem cell (CSC) population characterized with high aldehyde dehydrogenase activity in ovarian cancer cells, probably through disrupting the self-renewal capacity of CSCs. Low DDB2 expression correlates with poor outcomes among patients with ovarian cancer, as revealed from the analysis of publicly available gene expression array datasets. Given the finding that DDB2 protein expression is low in ovarian tumor cells, enhancement of DDB2 expression is a promising strategy to eradicate CSCs and would help to halt ovarian cancer relapse.