Downregulation of BRAF‑activated non‑protein coding RNA in patients with hepatitis B virus‑associated hepatocellular carcinoma

Abstract

Long non-coding RNAs (lncRNAs) have been investigated as a novel class of regulators of cellular processes, including cell growth, apoptosis and carcinogenesis. lncRNA BRAF-activated non-protein coding RNA (BANCR) has recently been revealed to be involved in tumorigenesis of numerous types of cancer, including papillary thyroid carcinoma, melanoma, non-small cell lung cancer and colorectal cancer. However, the expression profiles and biological relevance of lncRNA BANCR in hepatocellular carcinoma (HCC) has not yet been reported. In the present study, the expression level of BANCR in tumor tissues and para-cancerous tissues was determined by reverse transcription-quantitative polymerase chain reaction in patients with hepatitis B virus (HBV)-associated HCC, and its association with clinicopathological characteristics of patients was analyzed. The results demonstrated that the expression level of BANCR was significantly reduced in tumor tissues in comparison with in para-cancerous tissues (P<0.001). Furthermore, the present study demonstrated that BANCR expression level was closely associated with serum α-fetoprotein levels (P<0.01) and HCC tumor number (P<0.05). To the best of our knowledge, these results revealed for the first time that BANCR downregulated in patients with HBV-associated HCC and BANCR expression level may be a potential valuable diagnosis and therapeutic biomarker in HCC.

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) [22,35,36]. The NOS scores are presented in Table 2.…”

“…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][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 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.…”