OncoTargets and Therapy (May 2020)
lncRNA MALAT1 Promotes EMT Process and Cisplatin Resistance of Oral Squamous Cell Carcinoma via PI3K/AKT/m-TOR Signal Pathway
Abstract
Ran Wang,1,* Xinxing Lu,2,* Riyue Yu1 1Department of Stomatology, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Riyue Yu Email [email protected]: Cisplatin (DDP) is the first-line chemotherapy agent for the treatment of oral squamous cell carcinoma (OSCC). The emergence of DDP resistance leads to diminished drug efficacy and survival benefit. lncRNA MALAT1 has been considered as one of the most important factors in OSCC. It has also been reported to enhance chemo-resistance in other kinds of carcinomas. However, little is known about the role of lncRNA MALAT1 in DDP resistance of OSCC.Materials and Methods: Two kinds of human DDP-resistant cell lines (CAL-27R and SCC-9R) were developed from cisplatin-naïve cell lines (CAL-27 and SCC-9, respectively) as in vitro cell models. Cell transfection was performed to overexpress or knockdown MALAT1 in these cells. Mouse xenograft models were also established. The following measurements were performed: cell proliferation, colony formation, wound healing, transwell, and TUNEL assays, as well as Western blot and immunofluorescence staining.Results: DDP-resistant cells showed higher expression level of MALAT1 compared to cisplatin-naïve cells. The overexpression of MALAT1 in cisplatin-naïve cells enhanced DDP resistance and suppressed apoptosis in OSCC cells. However, the knockdown of MALAT1 in DDP-resistance cells induced apoptotic cell death and restored the sensitivity to DDP. Further analyses suggested that MALAT1 might promote DDP resistance via regulating P-glycoprotein expression, epithelial–mesenchymal transition process, and the activation of PI3K/AKT/m-TOR signaling pathway.Conclusion: MALAT1 might be a potential therapeutic target for the treatment of DDP-resistant OSCC.Keywords: oral squamous cell carcinoma, cisplatin resistance, lncRNA MALAT1, P-glycoprotein
