MicroRNAs modulate the expression of the SOX18 transcript in lung squamous cell carcinoma.

Abstract

Recent statistics show that lung cancer is the second most common malignant tumor in the world (14% of all cancers in the USA), both in terms of morbidity and mortality. The mortality of this type of tumor shows an increasing trend (28% for men and 26% for women). Lung squamous cell carcinoma(LSCC) is the second‑largest histological subtype of non‑small cell lung cancers(NSCLCs) after adenocarcinoma. SRY‑related HMG‑box18(SOX18) protein is an important transcription factor involved in the development of the cardiovascular system and the lymphatic ducts. In addition, it was observed that SOX18 functions in wound healing processes and the development of atherosclerosis. Likewise, an increased level of this protein was found in melanomas and malignant pancreatic, stomach and breast tumors. Furthermore, high expression of SOX18 in gastric cancer stromal cells was found to be associated with a poor patient prognosis. In the present study, we analyzed the expression of the SOX18 protein and the mRNA level in postoperative samples of LSCC and non‑malignant lung tissues(NMLTs), and a disparity in both levels was observed. Because of the fact that microRNAs(miRNAs) play important roles in the initiation and progression of lung cancer, the main aim of this study was to identify the miRNAs that interact with the SOX18 transcript in NSCLC cases. SOX18 mRNA expression level was significantly lower in the LSCC tissues than that noted in the NMLTs (p<0.01). However, protein levels were higher in the LSCC cases compared to these levels in the NMLTs (p<0.0001). We showed that miR‑7a and miR‑24‑3p were expressed more highly in the NMLTs than levels in the LSCC samples, and that they could be switched off in lung cancer tissue. Additionally, correlations between RQ‑values of SOX18 in NMLTs and LSCC samples (r=0.43, p=0.019), and between miR‑7a and miR24‑3p in NMLT cases (r=0.4, p=0.057) aswellas in the LSCC samples (r=0.51, p=0.012) were noted. In conclusion, miRNAs interact with the mRNA of the SOX18 gene, but the mechanism by which they could be inhibited in cancer cells requires further examination.