| Part1. Long non-coding RNA HRC is up-regulated and promotes cell proliferation and migration in clear cell renal cell carcinomaObjective: Emerging evidences indicate that long noncoding RNAs(lncRNAs) are eminent players in cancer biology. This study aimed to establish the role of regulation of new IncRNA NR 024373 (lncRNA HRC) on the proliferation and metastasis of clear cell renal cell carcinoma (ccRCC). Materials and methods: Quantitative real-time PCR (qRT-PCR) was used to detect IncRNA HRC expression level in 60 matched ccRCC tissues, 6 renal cancer cell lines, and 1 human normal kidney tubule epithelial cell line(HKC). Nuclear/cytoplasmic isolation essay was used to investigate the subcellular location of IncRNA HRC in ccRCC cell lines. Knockdown and overexpression studies were performed in 786-0 and Caki-2 cells using small-interfering-RNAs (siRNA) and lentiviral vector to evaluate the role of lncRNA HRC in cell proliferation, cell cycle control,and migration and invasion. Results: LncRNA HRC is a long intergenic RNA and cytoplasmic transcript, the genomic locus of lncRNA HRC is locate on chromosome 2q13.The expression of IncRNA HRC was significantly elevated in ccRCC tissues (3.77 fold)and cell lines (p< 0.001), high lncRNA HRC expression was significantly correlated with the tumor size (p=0.0056), Fuhrman grade (p=0.0002), tumor stage (p<0.0001), and lymph nodes metastasis (p=0.0384) of ccRCC. Knockdown of IncRNA HRC in higher-expressing 786-0 cells could significantly decrease proliferation and migration, and also promote G1 phase arrest compared with control group. While over-express of IncRNA HRC in lower-expressing Caki-2 cells produced the opposite results. Conclusions: Our study is the first to report IncRNA HRC function in cancer, we provides clinicopathological and experimental evidence that IncRNA HRC is a cytoplasmic transcript, and act as an oncogene in ccRCC. Silencing of lncRNA HRC inhibits cell growth, migration, and invasion, while overexpress of lncRNA HRC produce the opposite results, suggesting that targeting lncRNA HRC expression might be a promising therapeutic strategy for the treatment of ccRCC.Part2. LncRNAs act as prognostic and diagnostic biomarkers in renal cell carcinoma: a systematic review and meta-analysisObjective: To investigate the clinical values of long non-coding RNAs(lncRNAs) in RCC. Materials and methods: We conducted a systematic review and meta-analysis to investigate the clinical values, including clinicopathology, prognosis, and diagnosis of different IncRNAs in RCC. Results: A total of 14 eligible studies,including 10 on clinicopathological features,11 on prognosis, and 3 on diagnosis were identified. Results revealed that metastasis-associated lung adenocarcinoma transcript 1(MALAT1) expression was associated with tumor stage (odds ratio [OR], 3.46; 95%confidence interval [CI], 1.63-7.36; p=0.001). The high expression of MALAT1 could be considered a biomarker of the early detection of lymph node metastasis and predictor of poor survival in RCC patients, who likely manifested short overall survival (OS; hazard ratio [HR], 2.97; 95% CI, 1.68-5.28; p<0.001). For diagnostic value, the pooled results showed that lncRNA maintained a sensitivity of 0.89 and specificity of 0.91 in RCC diagnosis, The area under the curve of 0.94 (95% CI, 0.92-0.96) for IncRNAs in RCC diagnosis also indicated a significant advantage over other biomarkers. Conclusions:Our systematic review and meta-analysis demonstrated that IncRNAs could be considered biomarkers to detect lymph node metastasis and distant metastasis in early stages.LncRNAs could function as potential prognostic markers in RCC. LncRNAs could also display high accuracy for RCC diagnosis. |
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