Abstract. MicroRNA (miR)-137 has been reported to be underexpressed and involved in various cell processes and to have antitumor effects in a range of tumors, but so far not in renal cell carcinoma (RCC). The aim of the present study was to investigate the clinical significance and role of miR-137 in RCC. The expression levels of miR-137 were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in 50 cases of paired RCC tissues and adjacent normal tissues, and in RCC cell lines. The role of miR-137 in the growth and survival of RCC cells was assessed with several in vitro approaches and in nude mice models. The results of the RT-qPCR showed that the miR-137 expression was downregulated in the RCC tissues and cell lines. The in vitro assay showed that ectopic expression of miR-137 robustly impaired RCC cell proliferation, migratory and invasive properties, and increased the induction of cell apoptosis properties. The in vivo assay demonstrated that enforced miR-137 suppressed tumor growth in xenograft nude mice models. In addition, miR-137 was indicated to inhibit the activation of phosphoinositide 3 kinase/protein kinase B signal pathway, which contributes to the inhibition of RCC growth. These findings indicate that miR-137 functions as tumor suppressor in RCC, suggesting that miR-137 may be a potential therapeutic target for RCC.
IntroductionRenal cell carcinoma (RCC) accounts for 3% of all adult malignancies and is the third most common urological cancer worldwide, with the highest mortality rate of RCC at >40% (1). Approximately 65,150 novel cases and 13,680 mortalities were estimated for 2013 in the USA (1). Clear cell RCC (ccRCC) is the largest subtype of RCC and accounts for 70% of RCCs (2). Despite the increasingly early detection of RCC and more frequent use of surgery, the mortality rate has not changed significantly since 1990 and ~30% patients with localized RCC develop post-operative metastatic recurrence (3). The current adjuvant therapy for metastatic RCC remains extremely limited, as RCC is relatively unaffected by chemotherapy or radiotherapy (4). Therefore, a better understanding of the mechanisms involved in the pathogenesis of RCC and more effective therapeutic approaches are urgently required.MicroRNAs (miRNAs) are a small class of non-coding RNAs of 19-25 nucleotides in length. miRNAs are known to be important in the pathogenesis of cancer, from initiation to metastasis, primarily through interaction with the 3' untranslated region (3'UTR) of various target genes, which results in target gene translational silence or cleavage (5). miRNAs are known to be involved in multiple tumorigenic steps in human cancers, including in cell growth, apoptosis, migration and invasion (6-9). Of these miRNAs, miR-137 is an notable member that is located on chromosome 1p22 and has been indicated to be underexpressed in non-small lung (10), gastric (11), colorectal (12) and breast cancer (13). The restoration of miR-137 expression has been shown to inhibit cancer cell growth, mi...