Affiliations: [a] Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China | [b] Cancer Research Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China
Correspondence:
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Corresponding author: Wenyong Sun, Department of Pathology, Zhejiang Cancer Hospital, No. 38 Guangji Road, Hangzhou, Zhejiang, China. Tel.: +86 0571 88122222; E-mail: [email protected].
Abstract: BACKGROUND: Renal cell carcinoma (RCC) is the highest mortality rate of the genitourinary cancers, and the treatment options are very limited. Thus, identification of molecular mechanisms underlying RCC tumorigenesis, is critical for identifying biomarkers for RCC diagnosis and prognosis. OBJECTIVE: To validate whether the IGF-I/JAK2-STAT3/miR-21 signaling pathway is associated with human RCC cell growth. METHODS: qRT-PCR and Western blotting were used to detect the mRNA and protein expression levels, respectively. The MTT assay was performed to determine cell survival rate. The Annexin V-FITC/PI apoptosis detection kit was used to detect cell apoptosis. We employed RCC tissues and cell lines (A498; ACHN; Caki-1; Caki-2 and 786-O) in the study. IGF-I, and its inhibitor (NT-157) were administrated to detect the effects of IGF-I on the expression of miR-21 and p-JAK2. JAK2 inhibitor (AG490), and si-STAT3 were used to detect the effects of JAK2/STAT3 signaling pathway on the expression of miR-21. RESULTS: In our study, we firstly showed that the expression levels of IGF-I and miR-21 were up-regulated in RCC tissues and cell lines. After exogenous IGF-I treatment, the expression levels of miR-21, p-IGF-IR and p-JAK2 were significantly increased, whereas NT-157 treatment showed the reversed results. Further study indicated that JAK2 inhibitor or si-STAT3 significantly reversed the IGF-I-induced miR-21 expression level. Finally, we found that IGF-I treatment significantly prompted human RCC cell survival and inhibited cell apoptosis, and NT-157 treatment showed the reversed results. CONCLUSIONS: The IGF-I/JAK2-STAT3/miR-21 signaling pathway may be associated with human RCC cell growth.
