Decreased expression of BRAF-activated long non-coding RNA is associated with the proliferation of clear cell renal cell carcinoma

Abstract

BackgroundBRAF-activated long non-coding RNA (BANCR) has been associated with various types of cancer. Nevertheless, the role of BANCR in clear cell renal cell carcinoma (ccRCC) is still not fully understood. This study aims to investigate the relationship between ccRCC and BANCR.MethodsExpression of BANCR in TCGA renal cancer data sets was analyzed. The expression pattern of BANCR in Immortalized normal human proximal tubule epithelial cell line HK-2 and ccRCC cell lines (ACHN, CAKI-1, A498 and 786-O) was detected by real-time quantitative RT-PCR (qRT-PCR). ccRCC tissues with adjacent normal renal tissues diagnosed by pathological methods from 62 patients were used to detect the expression of BANCR, and its correlation with prognosis of ccRCC patients was assessed by Kaplan-Meier method. The LV-BANCR vector was used to examine the influence of BANCR on the proliferation, migration, invasion, apoptosis and cell cycle distribution of ccRCC cells in vitro.ResultsBANCR was downregulated in renal cancer according to TCGA data sets. Compared with adjacent normal renal tissues and normal human proximal tubule epithelial cell line HK-2, BANCR expression was significantly decreased in ccRCC tissues and ccRCC cell lines, and its low expression was associated with poor prognosis. Moreover, in the condition of BANCR overexpression by LV-BANCR vector, the proliferation, migration, invasion capacity of ccRCC cells was inhibited, while the apoptosis was increased and the G1 cell cycle arrest was induced in vitro.ConclusionsBANCR is downregulated in ccRCC tissues and cell lines, and is associated with ccRCC progression. Thus, BANCR may represent a novel prognostic biomarker and a potential therapeutic target for ccRCC patients.

High BANCR expression is associated with worse prognosis in human malignant carcinomas: an updated systematic review and meta-analysis

“…Nevertheless, there are some limitations in this meta-analysis: (a) most of the patients included in this study came from China, which may limit the generalizability of the results; (b) the sample size included was not large enough, which may affect the reliability of the results; (c) only 11 types of cancers were included to investigate the association between BANCR and cancer prognosis; thus, the conclusions of this study could not represent all cancers; (d) some HR values were extracted from survival curves, which may partly lead to extraction bias. [19] hepatocellular carcinoma up-regulation -Vimentin; E-Cadherin migration, invasion [17] up-regulation -Bcl-2; Bax; MEK; ERK; JNK; P38; cell invasion, proliferation and migration and apoptosis [14] up-regulationcell proliferation and migration [15] up-regulation -cell growth, migration and invasion [16] osteosarcoma up-regulation -ZEB1 apoptosis [11] papillary thyroid cancer downregulation -AKT; MEK; ERK; JNK; P38; proliferation, migration and invasiveness [24] downregulation -MAPK; PI3K-AKT cell growth, cycle and apoptosis [25,26] up-regulation -Raf; MEK; ERK; cell autophagy [27] colorectal cancer up-regulation -Vimentin; E-Cadherin; MEK; ERK; epithelial-mesenchymal transition (EMT) [34] up-regulation miR-203 CSE1L proliferation and invasion; cell sensitivity to adriamycin (ADR) [42] bladder cancer downregulation -apoptosis and migration [30] Malignant Melanoma up-regulation AKT; MEK; ERK; JNK; P38; cell proliferation and migration [31] breast cancer up-regulation -Bcl-2; Bax; PARP; Cleaved-caspase3 cell proliferation and invasion [33] up-regulation -Vimentin; E-Cadherin; MMP2; MMP9; MMP14 cell migration and invasion [32] clear cell renal cell carcinoma up-regulation -caspase3; caspase9; CDK4; CDK6 cell growth, cycle and apoptosis [18] Note: BRAF-activated noncoding RNA; MMP2, The matrix metalloproteinases 2; MMP9, The matrix metalloproteinases 9; MMP14: The matrix metalloproteinases 14; PARP: poly ADP-ribose polymerase; EMT, Epithelial-Mesenchymal Transition; ZEB1, zinc finger E-box binding homeobox 1; MAPK: Mitogen-activated protein kinase; ERK: extracellular signal-regulated kinase; JNK: Jun N-terminal kinases; CDK4: cyclin-dependent kinase 4; CDK6: cyclin-dependent kinase 6; NA, Not Available carcinoma; OS: Overall survival; DFS: Disease-free survival; RFS: Recurrencefree survival; OR: Odds ratio; HR: Hazard ratio; NOS: Newcastle-Ottawa scale; MMP2: Matrix metalloproteinase 2.; MMP9: Matrix metalloproteinase 9.; EMT: Epithelial-mesenchymal transition. ; ZEB1: Zinc finger E-box binding homeobox 1.; MAPK: Mitogen-activated protein kinase; ERK: Extracellular signal-regulated kinase; JNK: Jun N-terminal kinase; Random: Random-effects model; TNM: TNM stage; Fixed: Fixed-effects model…”

“…By using RNA-sequencing, Flockhart et al originally found that BRAF-activated noncoding RNA (BANCR), a 693-bp lncRNA located on chromosome 9, was overexpressed in melanoma cells. Additionally, accumulating studies have suggested that BANCR is correlated with the metastasis and invasion of multiple tumor cells and could function as a prognostic biomarker for cancers such as gastric cancer [ 12 , 13 ], hepatocellular carcinoma [ 14 – 17 ], renal cell carcinoma and non-small cell lung cancer [ 18 , 19 ]. However, due to the small sample size and discrepant conclusions among those studies, the association of BANCR expression with the prognosis of patients is still undefined.…”

High BANCR expression is associated with worse prognosis in human malignant carcinomas: An updated systematic review and meta-analysis

“…Of these 20 studies with 1997 patients, 19 studies with 1847 patients were from China, and 1 study comprising 150 patients was from Iran [22]. The publication years ranged from 2014 to 2019, and the expression levels of BANCR were all detected by qRT-PCR for the following cancer types: lung cancer [19], hepatocellular carcinoma [15][16][17], osteosarcoma [23], papillary thyroid cancer [24][25][26][27], gastrointestinal cancer [28,29], bladder cancer [30], malignant melanoma [31], breast cancer [32,33], clear cell renal cell carcinoma [18], esophageal squamous cell carcinoma and endometrial cancer (details in Table 1) [22,34,35]. The NOS scores are presented in Table 2.…”

“…By using RNA-sequencing, Flockhart et al originally found that BRAF-activated noncoding RNA (BANCR), a 693-bp lncRNA located on chromosome 9, was overexpressed in melanoma cells. Additionally, accumulating studies have suggested that BANCR is correlated with the metastasis and invasion of multiple tumor cells and could function as a prognostic biomarker for cancers such as gastric cancer [12,13], hepatocellular carcinoma [14][15][16][17], renal cell carcinoma and non-small cell lung cancer [18,19]. However, due to the small sample size and discrepant conclusions among those studies, the association of BANCR expression with the prognosis of patients is still unde ned.…”

Long Non-Coding RNA Emergence During Renal Cell Carcinoma Tumorigenesis

“…A 5-lncRNA signature including lncRNA-LET, PVT1, PANDAR, PTENP1, and lnc00963 can discriminate patients with clear cell RCC from healthy controls [91]. LncRNA TCL6, NBAT-1, SPRY4-IT1, RCCRT1, GAS5, and CADM1-AS1 have all been associated with poor prognosis in RCC patients [88,[92][93][94][95][96].…”