This study aimed to examine hypoxia-induced phenotypic alterations in ovarian cancer and to elucidate the molecular mechanisms mediated by long non-coding RNAs (lncRNAs). Transwell assay was used to assess migration and invasion, and methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was used to assess proliferation. Western blot analysis was conducted to evaluate the expression of factors associated with epithelial–mesenchymal transition (EMT). RNA sequencing was carried out to identify potential targets, and dual-luciferase and biotin-labeled microRNA (miRNA) pull-down assays were performed to identify interactions between these targets. Gain- and loss-of-function experiments were conducted to validate their effects. Hypoxia promoted the migration, invasion, and EMT of HO8910 and A2780 cells. Under hypoxic conditions, the expression of lncRNA-aspartyl-transfer RNA synthetase antisense RNA 1 (lnc- DARS-AS1 ) was significantly increased, and this upregulation exerted a proliferative effect on ovarian cancer cells. Furthermore, lnc- DARS-AS1 promoted solute carrier family 2 member 12 (SLC2A12) expression, accelerating ovarian cancer progression. Luciferase, biotin-labeled miRNA pull-down, and cellular function assays confirmed that lnc- DARS-AS1 binds to miR-378a-5p to enhance SLC2A12 levels. The expression levels of SLC2A12 were determined in samples from patients with ovarian cancer, and they showed a positive correlation with cancer progression. This research established that the lnc- DARS-AS1 /miR-378a-5p/SLC2A12 axis is involved in ovarian cancer progression under hypoxic conditions, providing new perspectives on the treatment and management of ovarian cancer.
Triple-negative breast cancer (TNBC) is a fatal disease. Drug resistance and the lack of effective drugs are the leading causes of death in patients with TNBC. Recently, long non-coding RNAs have been proven to be effective drug design targets owing to their high tissue specificity; however, an effective drug delivery system is necessary for their clinical application. In this study, we constructed a novel nanodrug delivery system based on the epidermal growth factor receptor (EGFR)-targeted aptamer CL4-modified exosomes (EXOs-CL4) for the targeted delivery of aspartyl-tRNA synthetase-antisense RNA 1 (DARS-AS1) small interfering RNA (siRNA) and doxorubicin (DOX) to TNBC cells in vitro and in vivo . This delivery system exerted potent anti-proliferation, anti-migration, and pro-apoptotic effects on TNBC cells. Silencing DARS-AS1 increased the sensitivity of TNBC cells to DOX by suppressing the transforming growth factor-β (TGF-β)/Smad3 signaling pathway-induced autophagy, thereby enhancing the synergetic antitumor effects. Collectively, our findings revealed that EXOs-CL4-mediated delivery of DARS-AS1 siRNA can be used as a new treatment strategy for DOX-resistant TNBC. Moreover, EXOs-CL4 can be used as effective drug delivery systems for targeted TNBC therapy.
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