Long non‑coding RNA KCNQ1OT1 promotes nasopharyngeal carcinoma cell cisplatin resistance via the miR‑454/USP47 axis

Abstract

Long non-coding RNAs serve an essential role in drug resistance in various types of cancer, including lung, breast and bladder cancer. The present study aimed to investigate whether KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) was associated with cisplatin (DDP) resistance in nasopharyngeal carcinoma (NPC). KCNQ1OT1, microRNA (miR)-454 and ubiquitin specific peptidase 47 (USP47) expression levels were measured via reverse transcription-quantitative PCR. 5-8F/DDP and SUNE-1/DDP cell viability and chemosensitivity were assessed by performing Cell Counting Kit-8 assays. Colony forming and Transwell assays were conducted to assess the effect of the KCNQ1OT1/miR-454/USP47 axis on DDP resistance in NPC cells. The association between miR-454 and KCNQ1OT1 or USP47 was verified via bioinformatics analysis, dual-luciferase reporter assays and RIP assays. KCNQ1OT1 and USP47 expression levels were significantly upregulated, whereas miR-454 expression levels were significantly downregulated in DDP-resistant NPC cells compared with parental NPC cells. KCNQ1OT1 knockdown promoted chemosensitivity in DDP-resistant NPC cells (5-8F/DDP and SUNE-1/DDP), as indicated by significantly decreased cell proliferation, migration and invasion in the short hairpin RNA (sh)KCNQ1OT1 group compared with the sh-negative control (NC) group. Moreover, miR-454 was identified as a target of KCNQ1OT1. KCNQ1OT1 overexpression significantly reversed miR-454 overexpression-mediated effects on NPC cell viability and DDP resistance. Furthermore, the results indicated that miR-454 directly targeted USP47. Compared with the shNC group, USP47 knockdown significantly suppressed NPC cell viability and DDP resistance, which was significantly reversed by co-transfection with miR-454 inhibitor. Furthermore, compared with the shNC group, KCNQ1OT1 knockdown significantly downregulated USP47 expression, which was significantly counteracted by miR-454 knockdown. Collectively, the results of the present study indicated that KCNQ1OT1 enhanced DDP resistance in NPC cells via the miR-454/USP47 axis, suggesting a potential therapeutic target for patients with DDP-resistant NPC.

The Role of lncRNAs in Rare Tumors with a Focus on HOX Transcript Antisense RNA (HOTAIR)

“…More recently, many other lncRNAs have been associated with NPC progression, with their capacity of sponging different microRNAs [ 58 , 61 , 62 , 63 , 71 , 72 , 73 , 74 ]. Additionally, in NPC patients, a large number of lncRNAs were also associated with cisplatin resistance [ 42 , 43 , 44 , 45 , 75 , 76 , 77 , 78 ] and radioresistance [ 54 , 79 , 80 ].…”

Involvement of Non-Coding RNAs in Chemo- and Radioresistance of Nasopharyngeal Carcinoma

“… 99 Existing research results indicated that KcNQ1OT1 enhanced DDP resistance in NPC cells via the miR‑454/USP47 axis, suggesting a potential therapeutic target for patients with DDP‑resistant NPC. 100 Wang et al demonstrated elevated expression levels of lncRNA SLC25A21-AS1 in NPC tissues and cells. In addition, high expression of SLC25A21-AS1 could target miR-324-3p and thus mediate IL-6, resulting in enhanced proliferation and multidrug resistance in NPC cells.…”

“…Therefore, KcNQ1OT1 might serve as a potential target for overcoming DDP resistance in NPC chemotherapy. 100 Wang et al showed that miR-181a could enhance the sensitivity of nasopharyngeal carcinoma cells to paclitaxel by promoting apoptosis, while in nasopharyngeal carcinoma, lncCCAT1 could directly bind to miR-181a, thus inhibiting the biological function of miR-181a and making nasopharyngeal carcinoma cells less sensitive to paclitaxel. 105 In addition, lnc SLC25A21-AS1 regulates IL-6 by targeting miR-324-3p, making nasopharyngeal carcinoma resistant to multiple chemotherapeutic agents.…”

Silencing LncRNA PVT1 Reverses High Glucose-Induced Regulation of the High Expression of PVT1 in HRMECs by Targeting miR-128-3p

“…With the gradual application of molecular technology to the diagnosis and prognostic treatment of diseases, long noncoding RNAs (ln-cRNAs) have developed into a new biomarker and therapeutic target for a variety of human diseases. LncRNAs are over 200 in length and have no protein coding ability, which are important regulatory factors involved in transcription, differentiation, invasion, apoptosis and other biological processes [13,14]. In existing studies, Thomas et al proved Silencing LncRNA PVT1 Reverses High Glucose-Induced Regulation of the High Expression of PVT1 in HRMECs by Targeting miR-128-3p…”