LINC00511 promotes the malignant phenotype of clear cell renal cell carcinoma by sponging microRNA-625 and thereby increasing cyclin D1 expression

Abstract

The expression pattern and detailed roles of long noncoding RNA LINC00511 in clear cell renal cell carcinoma (ccRCC) remain unknown. We measured LINC00511 expression in ccRCC. We clarified the clinical characteristics associated with LINC00511 in ccRCC. We examined the biological roles of LINC00511 in the progression of ccRCC, and we identified the potential mechanisms involved. LINC00511 was upregulated in ccRCC tissues and cell lines. High LINC00511 expression significantly correlated with TNM classification, lymph node metastasis, and short overall survival among patients with ccRCC. Additionally, LINC00511 knockdown restricted ccRCC cell proliferation, colony formation, and metastasis in vitro; accelerated cell cycle arrest at G0–G1 and apoptosis in vitro; and decreased tumor growth in vivo. Investigation of the mechanism revealed that LINC00511 directly interacted with microRNA-625 (miR-625), and the inhibitory effects of the LINC00511 knockdown on malignant characteristics were neutralized by miR-625 silencing. Furthermore, cyclin D1 (CCND1) was identified as a direct target of miR-625 in ccRCC cells. The tumor-suppressive activity of miR-625 upregulation on ccRCC cells was reversed by CCND1 reintroduction. In conclusion, LINC00511 serves as a competing endogenous RNA that regulates CCND1 expression by sponging miR-625 in ccRCC. Hence, the LINC00511/miR-625/CCND1 pathway might be a promising therapeutic target in ccRCC.

Prognostic significance of long intergenic non-protein-coding RNA 511expression in malignant tumors

“…Next, these 73 studies were carefully screened by the titles, abstracts, and full texts. Finally, a total of 13 eligible studies comprising 1053 cancer patients were included according to the inclusion and exclusion criteria in this meta-analysis [ 9 , 10 , 16 , 17 , 21 , 22 , 25 , 28 , 33 – 35 ] (Fig. 1 ).…”

“…[ 17 ] In thyroid cancer, Chen et al [ 37 ] revealed that LINC00511 could bind to TATA-box binding protein-associated factor 1 to activate Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway, which remarkably decreased the radio-sensitivity of malignant cells. In renal cell cancer cells, Deng et al [ 25 ] found that LINC00511 was capable of promoting the proliferation, colony formation, in vitro invasion, and in vivo tumor growth, as well as inhibit apoptosis of cancer cells, by repressing the miR-625 and consequently upregulating CCND1. [ 25 ] Collectively, these studies provide extensive evidences that LINC00511 may act as an oncogene in human malignancies, which strongly supported the findings of our meta-analysis.…”

“…In renal cell cancer cells, Deng et al [ 25 ] found that LINC00511 was capable of promoting the proliferation, colony formation, in vitro invasion, and in vivo tumor growth, as well as inhibit apoptosis of cancer cells, by repressing the miR-625 and consequently upregulating CCND1. [ 25 ] Collectively, these studies provide extensive evidences that LINC00511 may act as an oncogene in human malignancies, which strongly supported the findings of our meta-analysis.…”

“…[ 5 – 7 ] The long intergenic noncoding RNA 00511 ( LINC00511 ) was firstly identified in 2015 by Cabanski et al [ 8 ] Subsequently, several studies reported that abnormal LINC00511 expression was correlated with prognosis in patients with malignancies. Moreover, most studies suggested that LINC00511 could act as an oncogene and its high expression was predictive of poor prognosis in various malignancies, such as cervical cancer (CC), [ 9 , 10 ] ovarian cancer (OC), [ 11 – 13 ] hepatocellular carcinoma (HCC), [ 14 – 16 ] pancreatic cancer, [ 17 ] lung cancer, [ 18 , 19 ] breast cancer, [ 20 – 24 ] renal cancer, [ 25 ] and glioma. [ 26 , 27 ] Nevertheless, some studies also reported that LINC00511 could be a tumor suppressor, with high LINC00511 expression being associated with favorable prognosis of some cancer patients.…”

LINC00511 as a prognostic biomarker for human cancers: a systematic review and meta-analysis

“…LINC00511 is an oncogene which plays a negative regulatory role in cell proliferation, cell cycle progression, apoptosis, invasion, migration, metastasis and chemoresistance [15][16][17][18][19][20][21][22][23]. Noteworthily, overexpression of LINC00511 was shown to be a predictor for cancer prognosis [16,18,20,22,[24][25][26][27][28]. However, the results of the studies were not consistent.…”