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21 September 2015 : Clinical Research  

MiR-185-3p and miR-324-3p Predict Radiosensitivity of Nasopharyngeal Carcinoma and Modulate Cancer Cell Growth and Apoptosis by Targeting SMAD7

Jianhua XuABCD, Qin AiCDEF, Hanhai CaoDEFG, Quan LiuABCDEFG

DOI: 10.12659/MSM.895660

Med Sci Monit 2015; 21:2828-2836

Abstract

BACKGROUND: MiR-185-3p and miR-324-3p are 2 miRNAs that regulate nasopharyngeal carcinoma (NPC) radioresistance. This study tried to assess the clinical values of low miR-185-3p and low miR-324-3p expression in predicting response to radiotherapy (RT) and prognosis of NPC and to explore their new downstream targets.

MATERIAL AND METHODS: We recruited 80 patients with primary NPC. MiR-185-3p and miR-324-3p expression in the tumor tissues before and after RT or chemoradiotherapy (CRT) were determined. Overall survival and recurrence-free survival curves were estimated to assess the prognostic values of these 2 miRNAs. Their target was predicted using an online database and verified using dual luciferase assay, qRT-PCR, and Western blot analysis. In addition, the function of miR-185-3p/miR-324-3p-SMAD7 axis in NPC cells was investigated.

RESULTS: The expression of miR-185-3p and miR-324-3p was significantly reduced after RT in radioresistant but not in radiosensitive cases. Although miR-185-3p and miR-324-3p are not independent prognostic indicators of overall survival of NPC, their low expression is still associated with poor overall survival and recurrence-free survival. In addition, miR-185-3p and miR-324-3p can modulate growth and apoptosis of NPC cells, partly via SMAD7.

CONCLUSIONS: Combined low miR-185-3p and miR-324-3p might be important markers for prediction of low response to RT/CRT and poor overall survival and recurrence-free survival. MiR-185-3p and miR-324-3p can modulate NPC cell growth and apoptosis, at least partly through targeting SMAD7.

Keywords: Apoptosis - radiation effects, Cell Growth Processes - radiation effects, HEK293 Cells, MicroRNAs - genetics, Nasopharyngeal Neoplasms - radiotherapy, Radiation Tolerance - genetics, Smad7 Protein - genetics

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750