Bladder cancer is a heterogeneous disease with unpredictable clinical outcome. Several risk factors have been identified for bladder cancer, such as cigarette smoking, exposures to aromatic amines and 4,4'-methylenebis(2-chloroaniline) [19]. However, the molecular mechanisms underlying the bladder cancer development are still unclear. Nowadays, early screening and detection of bladder cancer remain a great challenge in clinic. Therefore, it is important to explore the effective bio-markers for early diagnosis of bladder cancer.
MiRNAs are a group of small endogenous RNAs, and they play regulatory role in gene expression at post-transcriptional level [9]. The expression profile of extracellular cell-free miRNAs are significantly correlated with tumor initiation, development and progression, which have been considered as promising biomarkers for cancer management [20]. The urinary miRNAs are stable at room temperature, and they could not be unaffected by multiple freeze-thaw cycles [21], indicating their properties as molecular biomarkers for cancer diagnosis and prognosis. Urine supernatant is a particularly desirable source of biomarkers for bladder cancer, with greatly convenient, reducing protein interference during RNA extraction and reflecting the status of diseases [22].
MiR-200c belongs to the miR-200 family which consists of miR-200a, miR-200b, miR-200c, miR-141 and miR-429 [23]. Accumulating evidences have demonstrated that miR-200 family has the capacity to regulate cancer transformation, growth, metastasis, and therapeutic response through targeting multiple signaling pathways, such as epithelial-mesenchymal transition (EMT), TGF-β signaling, PI3K/Akt signaling, Notch signaling, VEGF signaling, and NF-κB signaling [15, 24]. The expression pattern of miR-200c has been confirmed as a potential diagnostic and prognostic biomarker in a variety of tumors. For instance, Antolín et al. reported that circulating miR-200c was deregulated in breast cancer and showed close correlation with clinical characteristics of the patients that might serve as an independent prognostic indicator for the patients [25]. Meng et al. revealed that miR-200c level was involved in tumor progression and could distinguish malignant cases from benign ovarian tumors [26]. However, the clinical significance of miR-200c had been rarely reported in bladder cancer.
In the present study, qRT-PCR was applied to detect the relative expression level of miR-200c in 205 urine samples collected from 109 bladder cancer patients and 96 healthy controls. Urine miR-200c expression was obviously down-regulated in bladder cancer patients compared with healthy controls. Additionally, the decreased expression of miR-200c was negatively correlated with histological grade, tumor stage, and lymph node metastasis. All the data suggested that miR-200c as a tumor suppressor was involved in the progression and metastasis of bladder cancer patients. ROC analysis illustrated that urine miR-200c was an useful biomarker for early detection of bladder cancer. The conclusion was consistent with the previous studies. Wu et al. reported that the urinary miR-200 family levels were decreased in patients with bladder cancer [27]. The study carried out by Liu et al. showed that miR-200c could inhibit bladder cancer cells proliferation through down-regulating BMI-1 and E2F3 [28]. However, the possible underlying mechanisms for its participation in bladder cancer progression remained not clarify. Additionally, the sample size was relatively small that might influence the accuracy of our results. Therefore, further researches with a extended sample size will be performed to improve our conclusion.