Abstract

MicroRNAs play important roles in laryngeal carcinoma and other cancers. However, the expression of microRNAs in paracancerous tissue has been studied less. Here, using laser capture microdissection (LCM), we detected the expression of microRNAs in paracancerous tissues. Among all down-regulated microRNAs in the center area of tumor tissues, only miR-30b expression was significantly reduced in paracancerous tissues compared to surgical margins. Therefore, to further investigate the effect of miR-30b on laryngeal carcinoma, we stably overexpressed miR-30b in laryngeal carcinoma cell line HEp-2 cells. It was found that although there was no significant difference in cell viability between miR-30b overexpressed cells and control HEp-2 cells, p53 expression was obviously enhanced in miR-30b overexpressed cells. Whether miR-30b could improve the anti-tumor effect of adenovirus-p53 (Ad-p53) in laryngeal carcinoma and other cancer cell lines was also evaluated. It was found that in miR-30b overexpressed HEp-2 cells, p53-mediated tumor cell apoptosis was obviously increased both in vitro and in vivo. MDM2-p53 interaction might be involved in miR-30b-mediated anti-tumor effect. Together, results suggested that miR-30b could modulate p53 pathway and enhance p53 gene therapy-induced apoptosis in laryngeal carcinoma, which could provide a novel microRNA target in tumor therapy.

Highlights

  • Laryngeal carcinoma is one of the most aggressive cancers of the head and neck region

  • Tumor tissue sections (Figure 1A) from laryngeal carcinoma patients were divided into center area (Figure 1B, Area 4), paracancerous (Figure 1B, Area 1–3) and surgical margins by laser capture microdissection (LCM)

  • Using extracted RNA from different regions of tissue, RT-PCR results showed that in total detected microRNAs, only the expression of miR-30b was significantly down-regulated in paracancerous tissue compared with surgical margins (Table 1)

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Summary

Introduction

Laryngeal carcinoma is one of the most aggressive cancers of the head and neck region. The survival rate of patients with laryngeal carcinoma is low due to its resistance to chemotherapy/. Radiotherapy and frequent local or regional recurrence after surgery excision [1,2]. Residual tumor tissue has been previously considered to be one of the main causes which induce local recurrence post-surgery [2]. About 3.9%–32% of patients with laryngeal carcinoma develop local recurrences microscopically negative margins were defined [3]. A biological process called “field cancerization” has been introduced to demonstrate that a population of cells with early genetic changes (without histopathology) remains in paracancerous tissues, and was proposed to explain the locally recurrent cancer and multiple primary tumors [3,4]. Identification of the important molecular markers in these genetically transformed cells during field cancerization could be meaningful in the field of cancer therapy

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