An increased level of MiR-222-3p is associated with TMP2 suppression, ERK activation and is associated with metastasis and a poor prognosis in renal clear cell carcinoma
Affiliations: [a] Department of Urology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China | [b] Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang, Hangzhou, Zhejiang, China
Correspondence:
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Corresponding author: Qi Zhang, Department of Urology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou, Zhejiang 310014, China. Tel.: +86 571 85893311; Fax: +86 571 85893587; E-mail: zhangqi1@hmc.edu.cn.
Abstract: OBJECTIVE: Renal cell carcinoma (RCC) is the most common malignancy involving the kidneys and a major cause of cancer mortality. The involvement of microRNA (miRNA) expression in the tumorigenesis and progression of RCC still not been previously highlighted. We aimed to explore the potential role of miR-222-3p in renal cell carcinoma (RCC). METHOD: We first found that miR-222-3p was elevated significantly in the RCC tissues as compared to the non-tumor counterparts. We also found that a higher level of miR-222-3p in different RCC cell lines than the HK-2 cells. RESULTS:In vitro validation experiment using miR-222-3p mimic molecules significantly induced expression of EMT marker vimentin and downregulated E-cadherin in both 769-P and 786-O RCC cells. In contrary, when miR-222-3p was downregulated by its inhibitor, the reverse observations were made. We then demonstrated a reversal association between the expression level of miR-222-3p and TIMP2/ERK where TIMP2 functions as a tumor suppressor. In a small cohort of 45 clinical samples, we found that miR-222-3p expression level was elevated and was associated with a poorer survival of the patients. Patients with higher miR-222-3p expression showed had a statistically shorter overall survival than those patients of lower miR-222-3p level (HR, 5.789; p= 0.02). CONCLUSION: Collectively, we showed that miR-222-3p functioned as a tumor progression marker and could be a target for future drug development.
