MiR-21: A Non-invasive Biomarker and Potential Therapeutic Target for Lung Cancer?

Abstract

We read with great interest the article, published in Cell Biochem Biophys, showing that serum level of miR-21 was significantly elevated in lung cancer patients compared with controls. Receiver operating characteristic (ROC) curve analysis showed that miR-21 could differentiate lung cancer from healthy controls with an AUC (the area under the curve) of 0.85, and the optimal sensitivity and specificity were 85.7 and 86.5 %, respectively [1]. These findings suggest that miR-21 can be a potential non-invasive biomarker for lung cancer patients and miR-21 may be a potential therapeutic target for lung cancer. Lung cancer is one of the most common malignant tumors and is the leading cause of cancer mortality in the world [2]. Non-small cell lung cancer (NSCLC) accounts for approximately 80–85 % of all cases of lung cancer [3]. Despite much advances in lung cancer therapy, the survival rate for lung cancer patients remains very poor [4]. Recent advances in functional genomics provide an increasingly comprehensive portrayal of lung tumorigenesis, but the molecular pathogenesis of lung cancer remains poorly understood. These findings highlight the need for a better understanding of novel molecular mechanisms to guide treatment of lung cancer. MicroRNAs (miRNAs) are small non-coding RNAs that repress target gene expression by a combination of mRNA degradation and translation inhibition [5]. Recently, miR-21 expression was found to be higher in lung cancer serum samples than in control serum samples [3, 6–9]. High serum miR-21 was significantly correlated with tumor node metastases stage and lymph node metastasis of NSCLC patients [3, 5]. Overexpression of miR-21 showed a highly discriminative ROC curve profile, clearly distinguishing cancer patients from cancer-free subjects, and the detection of miR-21 expression yielded high sensitivity and specificity in the diagnosis of lung cancer [7–9]. Furthermore, miR-21 expression was elevated in human lung cancer cell lines (NCI-H446 and NCI-H460) [2]. Human mutS homolog 2 (hMSH2), one of the core mismatch repair genes, is affected in lung cancer development. Zhong et al. [2] found that hMSH2 was directly regulated by miR-21, and miR-21 expression was inversely correlated with hMSH2 expression in human lung cancer cell lines [2]. Notably, upregulation of miR-21 markedly promoted cell proliferation and revealed a higher proportion of cells at S phase. However, knockdown of miR-21 expression led to cell cycle arrest at G2/M phase and inhibited cell proliferation [2]. Similarly, tumor tissues showed an inverse correlation between high expression of miR-21 and low amounts of PTEN protein, where miR-21 suppresses PTEN by direct binding to the 30-UTR of PTEN [5]. Lung cancer cell lines (A549, H1703, and 801D) transfected with miR-21 inhibitor showed decreased endogenous miR-21 levels but significantly increased PTEN protein expression [5]. In addition, A549 and H1703 cells transfected with miR-21 inhibitor could restrain the growth of A549 and H1703 cells, and downregulation of miR-21 with miR-21 inhibitor in 801D cells could restrain its invasion ability [5]. Collectively, available evidence suggests that miR-21 may be a good biomarker for detection of lung cancer, and miR-21 may play an important role in lung cancer. However, further studies, especially in human systems, are needed to comprehensively explore the role of miR-21 in lung cancer, and miR-21 may be a potential therapeutic target for lung cancer. S.-C. Wang (&) Y.-F. Zhang Q. Xie PET/CT Center, Anhui Provincial Hospital, 17 Lujiang Road, Hefei 230001, Anhui, People’s Republic of China e-mail: wangsc3329@163.com