Xuan He

Cancer-Derived Exosomal miR-651 as a Diagnostic Marker Restrains Cisplatin Resistance and Directly Targets ATG3 for Cervical Cancer

Objective. Cancer-derived exosomes can facilitate drug resistance in cervical cancer. However, the mechanisms remain elusive. Herein, we observed the roles of exosomal miR-651 in cisplatin resistance of cervical cancer. Methods. Circulating miR-651 was detected in cervical cancer and healthy individuals. The diagnostic efficacy was determined. When transfected with miR-651 mimics, cisplatin resistance, apoptosis, and proliferation were assessed. The cancer-derived exosomes were separated and identified. We observed the uptake of PKH67-labeled exosomes by HeLa/S cells. After coculture with exosomes secreted by HeLa/S or HeLa/DDP cells, malignant behaviors were examined in HeLa/S cells. The interactions between ATG3 and miR-651 were validated by dual luciferase report. Biological behaviors were investigated for HeLa/S cells cocultured with exosomes secreted by miR-651 mimic-transfected HeLa/DDP cells. Results. Downregulated circulating miR-651 was found in cancer subjects than healthy individuals. It possessed high sensitivity and accuracy in diagnosing cervical cancer ( AUC = 0.9050 ). Lower miR-651 expression was confirmed in HeLa/DDP than HeLa/S cells. Forced miR-651 lessened cisplatin resistance and proliferation and elevated apoptosis in HeLa cells. ATG3 was a direct target of miR-651. The exosomes isolated from HeLa cells were rich in CD63, CD9, and CD81 proteins, thereby identifying the isolated exosomes. Exosomes secreted by HeLa/DDP cells can be absorbed by HeLa/S cells. When being cocultured with exosomes secreted by HeLa/DDP cells, malignant behaviors of HeLa/S cells were enhanced, which were ameliorated by miR-651 mimic exosomes. Conclusion. Our findings showed that cancer-derived exosomal miR-651 restrained cisplatin resistance and directly targeted ATG3, indicating that exosomal miR-651 could be a therapeutic agent.

GLTP Is a Potential Prognostic Biomarker and Correlates with Immunotherapy Efficacy in Cervical Cancer

Cervical cancer (CC) is the fourth most commonly diagnosed cancer in women worldwide. The prognosis of CC patients remains poor. The objective of our study was to explore the potential of glycolipid transfer protein (GLTP) in predicting the prognosis of CC and patients’ response to immunotherapy. The expression of GLTP was determined using TCGA and GEO datasets. The prognostic value of GLTP in CC patients was analyzed using Kaplan-Meier analysis and multivariate analysis. The relationships between BTBD10 and immunological checkpoints, immune checkpoint genes, and ferroptosis-related genes were analyzed to explore the impact of GLTP on CC immunotherapy. According to the dysregulated expressions of BTBD10, the IC50 distribution of various targeted medicines was studied. In this study, we found that GLTP expression was distinctly upregulated in CC specimens. However, Kaplan-Meier assays showed that CC patients with low GLTP expressions tended to exhibit a shorter overall survival. Importantly, multivariate assays revealed that GLTP expression was an independent prognostic factor for CC patients. Moreover, we observed that GLTP expression was related to CD4+ T cells, macrophages, and dendritic cells (DCs). Meanwhile, GLTP expressions were associated with those of immune checkpoints, ferroptosis-related genes, and m6A-related genes. The IC50 of Cisplatin, Docetaxel, and Paclitaxel was lower in the high-GLTP-expressing group. Taken together, GLTP was expected to be a prognostic and immunotherapeutic marker for CC.