Abstract
BackgroundClear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma subtype with a poor prognosis. LncRNA-LET is a long non-coding RNA (lncRNA) that is down-regulated in ccRCC tissues. However, its role in ccRCC development and progress is unclear.MethodsLncRNA-LET expression was detected in ccRCC tissues and ccRCC cells using quantitative real-time PCR. The overexpression and knockdown experiments were performed in ccRCC cells and xenograft mouse model to evaluate role of lncRNA-LET. Cell cycle, apoptosis and JC-1 assays were conducted via flow cytometer. The protein levels were measured through western blot analysis and the interaction between lncRNA-LET and miR-373-3p was identified via luciferase reporter assay.ResultsLncRNA-LET expression was lower in ccRCC tissues than that in the matched adjacent non-tumor tissues (n = 16). In vitro, lncRNA-LET overexpression induced cell cycle arrest, promoted apoptosis and impaired mitochondrial membrane potential, whereas its knockdown exerted opposite effects. Moreover, we noted that lncRNA-LET may act as a target for oncomiR miR-373-3p. In contrast to lncRNA-LET, miR-373-3p expression was higher in ccRCC tissues. The binding between lncRNA-LET and miR-373-3p was validated. Two downstream targets of miR-373-3p, Dickkopf-1 (DKK1) and tissue inhibitor of metalloproteinase-2 (TIMP2), were positively regulated by lncRNA-LET in ccRCC cells. MiR-373-3p mimics reduced lncRNA-LET-induced up-regulation of DKK1 and TIMP2 levels, and attenuated lncRNA-LET-mediated anti-tumor effects in ccRCC cells. In vivo, lncRNA-LET suppressed the growth of ccRCC xenograft tumors.ConclusionThese findings indicate that lncRNA-LET plays a tumor suppressive role in ccRCC by regulating miR-373-3p.
Highlights
Clear cell renal cell carcinoma is the most common renal cell carcinoma subtype with a poor prognosis
LncRNA‐LET expression is down‐regulated in Clear cell renal cell carcinoma (ccRCC) tissues To examine the clinical significances of long non-coding RNA (lncRNA)-LET in ccRCC tissues, we conducted quantitative real-time PCR
The lncRNA-LET expression level was significantly decreased in ccRCC tissues compared with matched adjacent non-tumor tissues (Fig. 1a)
Summary
Clear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma subtype with a poor prognosis. LncRNA-LET is a long non-coding RNA (lncRNA) that is down-regulated in ccRCC tissues. Renal cell carcinoma (RCC), as one of most frequent cancers worldwide, is a common lethal malignancy [1, 2]. RCC includes more than 10 histological and molecular subtypes [7], Non-coding RNAs (ncRNAs) are found to be important players in epigenetic regulation, especially long ncRNAs (> 200 nucleotides, lncRNAs) and microRNAs (< 22 nucleotides, miRNAs) [9,10,11]. LncRNA-LET, as a recently identified lncRNA, was located at chromosome 15q24.1 [11, 14], and it plays a suppressive role in regulating cancer cell growth in malignancies, including esophageal squamous cell carcinoma and lung adenocarcinoma [14,15,16].
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