The Non-Coding RNAs Inducing Drug Resistance in Ovarian Cancer: A New Perspective for Understanding Drug Resistance.

Ovarian cancer, a common malignant tumor, is one of the primary causes of cancer-related deaths in women. Systemic chemotherapy with platinum-based compounds or taxanes is the first-line treatment for ovarian cancer. However, resistance to these chemotherapeutic drugs worsens the prognosis. The underlying mechanism of chemotherapeutic resistance in ovarian cancer remains unclear. Non-coding RNAs, including long non-coding RNAs, microRNAs, and circular RNAs, have been implicated in the development of drug resistance. Abnormally expressed non-coding RNAs can promote ovarian cancer resistance by inducing apoptosis inhibition, protective autophagy, abnormal tumor cell proliferation, epithelial-mesenchymal transition, abnormal glycolysis, drug efflux, and cancer cell stemness. This review summarizes the role of non-coding RNAs in the development of chemotherapeutic resistance in ovarian cancer, including their mechanisms, targets, and potential signaling pathways. This will facilitate the development of novel chemotherapeutic agents that can target these non-coding RNAs and improve ovarian cancer treatment.

The Road of Solid Tumor Survival: From Drug-Induced Endoplasmic Reticulum Stress to Drug Resistance.

Endoplasmic reticulum stress (ERS), which refers to a series of adaptive responses to the disruption of endoplasmic reticulum (ER) homeostasis, occurs when cells are treated by drugs or undergo microenvironmental changes that cause the accumulation of unfolded/misfolded proteins. ERS is one of the key responses during the drug treatment of solid tumors. Drugs induce ERS by reactive oxygen species (ROS) accumulation and Ca2+ overload. The unfolded protein response (UPR) is one of ERS. Studies have indicated that the mechanism of ERS-mediated drug resistance is primarily associated with UPR, which has three main sensors (PERK, IRE1α, and ATF6). ERS-mediated drug resistance in solid tumor cells is both intrinsic and extrinsic. Intrinsic ERS in the solid tumor cells, the signal pathway of UPR-mediated drug resistance, includes apoptosis inhibition signal pathway, protective autophagy signal pathway, ABC transporter signal pathway, Wnt/ß-Catenin signal pathway, and noncoding RNA. Among them, apoptosis inhibition is one of the major causes of drug resistance. Drugs activate ERS and its downstream antiapoptotic proteins, which leads to drug resistance. Protective autophagy promotes the survival of solid tumor cells by devouring the damaged organelles and other materials and providing new energy for the cells. ERS induces protective autophagy by promoting the expression of autophagy-related genes, such as Beclin-1 and ATG5-ATG12. ABC transporters pump drugs out of the cell, which reduces the drug-induced apoptosis effect and leads to drug resistance. In addition, the Wnt/ß-catenin signal pathway is also involved in the drug resistance of solid tumor cells. Furthermore, noncoding RNA regulates the ERS-mediated survival and death of solid tumor cells. Extrinsic ERS in the solid tumor cells, such as ERS in immune cells of the tumor microenvironment (TME), also plays a crucial role in drug resistance by triggering immunosuppression. In immune system cells, ERS in dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) influences the antitumor function of normal T cells, which results in immunosuppression. Meanwhile, ERS in T cells can also cause impaired functioning and apoptosis, leading to immunosuppression. In this review, we highlight the core molecular mechanism of drug-induced ERS involved in drug resistance, thereby providing a new strategy for solid tumor treatment.

Recombinant human neuregulin-1ß is protective against radiation-induced myocardial cell injury.

The aim of the present study was to investigate the role of recombinant human neuregulin-1ß (rhNRG-1ß) in the repair of the radiation-induced damage of myocardial cells and the underlying mechanism. Rats were divided into the radiotherapy alone group, the rhNRG-1ß group (radiotherapy with rhNRG­1ß treatment) and the Herceptin group (radiotherapy with Herceptin treatment), and their myocardial cells were analyzed. The morphology of the myocardial cells was observed under an optical microscope, and the expression of γ­H2AX and p53 was analyzed using immunohistochemistry and western blot analysis. Damage to the myocardial cells was identified in the three groups following radiation treatment, which was identified by cell swelling and altered morphology. The integrated optical density values of γ­H2AX in the radiotherapy alone, rhNRG­1ß and Herceptin groups were 50.96±5.548, 27.63±10.61 and 76.12±2.084, respectively. The OD of the radiotherapy alone group was significantly higher than that of the rhNRG­1ß treated group (P<0.0001), and the value of the Herceptin group was significantly higher than that of the radiotherapy alone group (P<0.0001). The p53 level in the rhNRG­1ß group was less than that of the radiotherapy alone group (P<0.001), and was higher in the Herceptin group compared with the radiotherapy alone group (P<0.0001). Thus, rhNRG­1ß can ameliorate radiotherapy-induced myocardial cell injury, predominantly by enhancing myocardial cell DNA repair, inhibiting cell apoptosis and improving myocardial function. The results of this study in myocardial cells suggest that patients with thoracic cancer may benefit from treatment with rhNRG­1ß for the repair of the radiation-induced damage of myocardial cells.