Background: Urothelial bladder cancer (UBC) is one of the most lethal urological malignancies in the world. Patients with UBC are routinely given chemotherapy which results in a median survival of 12-15 months. Nuclear-enriched abundant transcript 1 (NEAT1) functions as an oncogene and could be used as a therapeutic target for human UBC. However, the involvement of NEAT1 in doxorubicin (DOX) resistance of UBC has been poorly demonstrated. Methods: Quantitative Real-time PCR (qRT-PCR) was used to detect the expression levels of NEAT1 and miR-214-3p in UBC tissues and cells. Bioinformatics prediction, RNA pull-down and qRT-PCR were used to assay the regulation manner of NEAT1 and miR-214-3p. Loss/gain function of NEAT1 and miR-214-3p together with western blot, drug resistance assay and flow cytometry were used to explore the influence of NEAT1 in DOX resistance was correlative with miR-214-3p. Finally, luciferase assay system was applied to determine the Wnt/β-catenin signal activity. Results: NEAT1 was upregulated and miR-214-3p was downregulated in DOX-resistant UBC tissues and cells. NEAT1 knockdown inhibited J82 and T24 cells to DOX chemosensitivity by negatively regulating miR-214-3p expression. NEAT1/miR-214-3p contributed to DOX resistance of UBC preliminary through the Wnt/β-catenin pathway. Conclusion: NEAT1 contributed to DOX resistance of UBC through the Wnt/β-catenin pathway partly by negatively regulating miR-214-3p expression. Our findings will provide a promising ncRNA targeted therapeutic strategy for UBC with DOX resistance.

Background: Long non-coding RNAs (lncRNAs) are implicated in cancer-related biological processes such as cell proliferation, cell cycle progression, cell migration, cell invasion, and chemoresistance. However, the effects of the lncRNA ZEB1-AS1 on oral squamous cell carcinoma (OSCC) have not been adequately demonstrated. The aims of our current study were to explore the roles of lncRNA ZEB1-AS1 in OSCC progression to reveal the potential mechanism. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure relative ZEB1-AS1 expression levels in OSCC tissues and adjacent non-cancerous tissues. The biological functions of ZEB1-AS1 in OSCC growth and progression were identified by cell proliferation, wound healing, and in vitro transwell assays as well as in vivo xenograft model. The underlying mechanism was detected with a dual-luciferase reporter (DLR) assay. Results: The up-regulation of ZEB1-AS1 and downregulation of miR-23a-3p (miR-23a) were found in OSCC cancer tissues. A ZEB1-AS1 knockdown remarkably suppressed in vitro cancerous, biological processes of OSCC cell lines such as cell proliferation, invasion, migration, and epithelial–mesenchymal transition (EMT). The tumor growth was also inhibited by silencing ZEB1-AS1 in vivo, and a DLR assay confirmed the association between ZEB1-AS1 and miR-23a. Conclusion: The newly identified lncRNA ZEB1-AS1 functions as a tumor promoter in OSCC through regulation of miR-23a. Based on these results, ZEB1-AS1 could be a valid molecular target for treating oral cancer.

Intrinsic or developing resistance to chemotherapy drugs including cisplatin (CDDP) remains the major limitation of cancer therapeutic efficacy in cancers. Recently, increasing evidence suggested that long noncoding RNAs (lncRNAs) play a critical role in various biological processes of tumors, and have been implicated in resistance to various drugs. However, the role of lncRNAs in cisplatin resistance is poorly understood. Here, we found that the expression of lncRNA CEBPA-DT/CEBPA/BCL2 was upregulated in cisplatin resistance OSCC cells (Cal27-CisR and HSC4-CisR) compared with their parental cells (Cal27 and HSC4). CEBPA-DT overexpression could upregulated both cytoplasmic and nuclear CEBPA expression. Down-regulation of CEBPA-DT enhances cisplatin sensitivity, facilitates cell apoptosis in cisplatin-resistant OSCC cells. In addition, we identified that CEBPA-DT regulates cisplatin chemosensitivity through CEBPA/BCL2-mediated cell apoptosis. Knockdown of CEBPA and BCL2 could alleviate the increasement of cisplatin resistance induced by CEBPA-DT overexpression. Our findings indicate that downregulation of lncRNA CEBPA-DT may be a potential therapy to overcome cisplatin resistance in OSCC.