Genome-Wide Analyses of Radioresistance-Associated miRNA Expression Profile in Nasopharyngeal Carcinoma Using Next Generation Deep Sequencing

Abstract

BackgroundRapidly growing evidence suggests that microRNAs (miRNAs) are involved in a wide range of cancer malignant behaviours including radioresistance. Therefore, the present study was designed to investigate miRNA expression patterns associated with radioresistance in NPC. MethodsThe differential expression profiles of miRNAs and mRNAs associated with NPC radioresistance were constructed. The predicted target mRNAs of miRNAs and their enriched signaling pathways were analyzed via biological informatical algorithms. Finally, partial miRNAs and pathways-correlated target mRNAs were validated in two NPC radioreisitant cell models. Results50 known and 9 novel miRNAs with significant difference were identified, and their target mRNAs were narrowed down to 53 nasopharyngeal-/NPC-specific mRNAs. Subsequent KEGG analyses demonstrated that the 53 mRNAs were enriched in 37 signaling pathways. Further qRT-PCR assays confirmed 3 down-regulated miRNAs (miR-324-3p, miR-93-3p and miR-4501), 3 up-regulated miRNAs (miR-371a-5p, miR-34c-5p and miR-1323) and 2 novel miRNAs. Additionally, corresponding alterations of pathways-correlated target mRNAs were observed including 5 up-regulated mRNAs (ICAM1, WNT2B, MYC, HLA-F and TGF-β1) and 3 down-regulated mRNAs (CDH1, PTENP1 and HSP90AA1).ConclusionsOur study provides an overview of miRNA expression profile and the interactions between miRNA and their target mRNAs, which will deepen our understanding of the important roles of miRNAs in NPC radioresistance.

Effects of irradiation on radioresistance, HOTAIR and epithelial-mesenchymal transition/cancer stem cell marker expression in esophageal squamous cell carcinoma

“…As a result, different radioresistant cell models, including MGR2R glioma cells (24), nasopharyngeal carcinoma cells (25) and ESCC cells (26) have been generated using distinct exposure to ionizing radiation in order to improve our understanding of radioresistance mechanisms. In the present study, an Eca109R60/2Gy cell model was established from parental Eca109 cells by repeated exposure to 2 Gy ionizing radiation.…”

Knockdown of microRNA-1323 restores sensitivity to radiation by suppression of PRKDC activity in radiation-resistant lung cancer cells

“…In our opinion, the gradually increasing doses of IR exposure decreased the potential for cellular contamination after repeated low-dose IR exposure and avoided sudden cell death during sublethal IR exposure. However, the manner in which IR exposure can maximally enhance the radioresistant capability remains to be investigated in the future (10).…”

“…Our results demonstrated that 18 known miRNAs were downregulated and 25 known miRNAs were upregulated. Some of the previously identified miRNAs have been reported to regulate the proliferation, apoptosis, migration and invasion of cancer cells and have prognostic value (10).…”

“…In the last decade, miRNAs, a new class of molecules able to post-transcriptionally regulate gene expression, have emerged to be involved in several fundamental physiological and pathological biomolecular and cellular mechanisms (8,9). miRNA profiles have been analyzed and several differentially expressed miRNAs involved in many cellular functions such as apoptosis, cell cycle control, and DNA damage/repair were identified in response to different radiation doses (10).…”

Overexpression of β-Catenin Decreases the Radiosensitivity of Human Nasopharyngeal Carcinoma CNE-2 Cells

“…Currently, radiotherapy remains the treatment of choice for NPC, and concomitant chemoradiotherapy has been proved to increase the survival [5,6]. Although 80% to 90% 5-year local control rates are achieved for NPC, there are still 20% to 30% of patients developing distal metastasis [7], and radioresistance has been identified as a major cause of therapeutic failure [8][9][10]. Elucidation of the mechanisms underlying the radioresistance in NPC is therefore beneficial for the individualized treatment for NPC.…”