LncRNA RP11-436H11.5, functioning as a competitive endogenous RNA, upregulates BCL-W expression by sponging miR-335-5p and promotes proliferation and invasion in renal cell carcinoma

Molecular Cancer, Oct 2017

Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play a crucial role in tumorigenesis. Here, we report a novel lncRNA, RP11-436H11.5, that regulates renal cell carcinoma (RCC) cell proliferation and invasion by sponging miR-335-5p. Expression of lncRNA RP11-436H11.5 was determined by a qRT-PCR assay in RCC tissues. RCC cell proliferation and invasion were measured by a cell proliferation assay and a transwell invasion assay. Expression of BCL-W was detected by a western blot assay. Interactions between lncRNA RP11-436H11.5 and miR-335-5p were measured by a luciferase reporter assay and a RNA-pull down assay. In vivo experiments were used to detect tumor formation. In this study, the qRT-PCR results illustrated that lncRNA RP11-436H11.5 was more highly expressed in RCC tissues than in adjacent normal renal tissues. The results of survival analysis indicated that patients in the high lncRNA RP11-436H11.5 group presented significantly worse outcomes compared with those in the low lncRNA RP11-436H11.5 group. Downregulation of lncRNA RP11-436H11.5 suppressed RCC cell proliferation and invasion in vitro and in vivo. Luciferase reporter assay results demonstrated that lncRNA RP11-436H11.5 enhanced BCL-W expression by regulating miR-335-5p expression. LncRNA RP11-436H11.5 could function as a miR-335-5p decoy to derepress expression of BCL-W. LncRNA RP11-436H11.5 could function as a competing endogenous RNA to promote RCC cell proliferation and invasion, which might serve as a therapeutic application to suppress RCC progression.

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LncRNA RP11-436H11.5, functioning as a competitive endogenous RNA, upregulates BCL-W expression by sponging miR-335-5p and promotes proliferation and invasion in renal cell carcinoma

Wang et al. Molecular Cancer LncRNA RP11-436H11.5, functioning as a competitive endogenous RNA, upregulates BCL-W expression by sponging miR-335-5p and promotes proliferation and invasion in renal cell carcinoma Kefeng Wang 0 Wei Jin 0 Yan Song 0 Xiang Fei 0 0 Department of Urology, Shengjing Hospital of China Medical University , Shenyang 110004 , China Background: Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play a crucial role in tumorigenesis. Here, we report a novel lncRNA, RP11-436H11.5, that regulates renal cell carcinoma (RCC) cell proliferation and invasion by sponging miR-335-5p. Methods: Expression of lncRNA RP11-436H11.5 was determined by a qRT-PCR assay in RCC tissues. RCC cell proliferation and invasion were measured by a cell proliferation assay and a transwell invasion assay. Expression of BCL-W was detected by a western blot assay. Interactions between lncRNA RP11-436H11.5 and miR-335-5p were measured by a luciferase reporter assay and a RNA-pull down assay. In vivo experiments were used to detect tumor formation. Results: In this study, the qRT-PCR results illustrated that lncRNA RP11-436H11.5 was more highly expressed in RCC tissues than in adjacent normal renal tissues. The results of survival analysis indicated that patients in the high lncRNA RP11-436H11.5 group presented significantly worse outcomes compared with those in the low lncRNA RP11-436H11.5 group. Downregulation of lncRNA RP11-436H11.5 suppressed RCC cell proliferation and invasion in vitro and in vivo. Luciferase reporter assay results demonstrated that lncRNA RP11-436H11.5 enhanced BCL-W expression by regulating miR-335-5p expression. LncRNA RP11-436H11.5 could function as a miR-335-5p decoy to derepress expression of BCL-W. Conclusions: LncRNA RP11-436H11.5 could function as a competing endogenous RNA to promote RCC cell proliferation and invasion, which might serve as a therapeutic application to suppress RCC progression. Non-coding RNAs; RP11-436H11; 5; miR-335-5p; Competitive endogenous RNA; Renal cell carcinoma Background Renal cell carcinoma (RCC) is the sixth most common malignant tumor in the United States, representing approximately 5% of adult male malignancies in 2017 [ 1 ]. The mortality of RCC patients appears to be increasing each year, resulting in frequent studies on biological detections and treatments [ 2 ]. Drug targeted therapies, including mammalian targets of rapamycin and vascular endothelial growth factor, have boomed [ 3, 4 ]. Unfortunately, drug resistance can occur in late stage patients, resulting in a bad prognosis [ 5, 6 ]. Therefore, the molecular mechanisms of RCC tumorigenesis need to be thoroughly investigated. Long non-coding RNAs (lncRNAs) are a set of nonprotein coding transcripts longer than 200 nucleotides [ 7 ]. They have been shown to have various functions including post-transcriptional regulation, chromatin modification and other biological processes [ 8, 9 ]. Some lncRNAs have been shown to play crucial roles in different kinds of cancer cells, including breast [10], colorectal [ 11 ], gastric [ 12 ] and renal [ 13 ] cancer cells. microRNAs (miRNAs) are also non-coding RNAs (ncRNAs) that are well known to play important roles in tumor biological processes [ 14, 15 ]. Effective diagnostic and therapeutic strategies have been used in clinical settings worldwide. Recently, a new mechanism was discovered in which some lncRNAs and mRNAs could interact with each other by competing with some common miRNAs [16]. In this case, lncRNAs could function as competing endogenous RNA (ceRNA) to sponge related microRNAs for the derepression of downstream genes at a post-transcriptional level [ 17, 18 ]. This mechanism provides a new way to study ncRNAs in tumors. Our previous study indicated that miR-335 could function as a tumor suppressor in RCC. Expression of miR-335 was downregulated in RCC tissues compared to corresponding normal renal tissues. Low expression of miR-335 was associated with tumor size, lymph node metastasis and T stage. miR-335 could inhibit proliferation and invasion through direct suppression of BCL-W [ 19 ]. Whether lncRNAs could regulate miR-335 to influence the biological behaviors of RCC cells has not been characterized. Here, we first identified a novel lncRNA, RP11436H11.5, that was more highly expressed in RCC tissues than in paired normal renal tissues. Downregulation of lncRNA RP11-436H11.5 could result in significant suppression of proliferation and invasion in vitro and in vivo. Our data demonstrated that lncRNA RP11436H11.5 could directly bind with miR-335-5p and function as a miRNA decoy to regulate BCL-W expression. Methods Clinical samples Human RCC tissues and adjacent normal renal tissues were acquired from patients diagnosed with RCC in the Department of Urology, Shengjing Hospital of China Medical University. The ethics consents were signed by each patient before the study. All patients agreed th (...truncated)


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Kefeng Wang, Wei Jin, Yan Song, Xiang Fei. LncRNA RP11-436H11.5, functioning as a competitive endogenous RNA, upregulates BCL-W expression by sponging miR-335-5p and promotes proliferation and invasion in renal cell carcinoma, Molecular Cancer, 2017, pp. 1, Volume 16, Issue 1, DOI: 10.1186/s12943-017-0735-3