Role of lncRNA BANCR in Human Cancers: An Updated Review

Abstract

Being located in a gene desert region on 9q21.11-q21.12, BRAF-activated non-protein coding RNA (BANCR) is an lncRNA with 693 bp length. It has been discovered in 2012 in a research aimed at assessment of gene expression in the melanocytes in association with BRAF mutation. Increasing numbers of studies have determined its importance in the tumorigenesis through affecting cell proliferation, migration, invasion, apoptosis, and epithelial to mesenchymal transition. BANCR exerts its effects via modulating some tumor-related signaling pathways particularly MAPK and other regulatory mechanisms such as sponging miRNAs. BANCR has been up-regulated in endometrial, gastric, breast, melanoma, and retinoblastoma. Conversely, it has been down-regulated in some other cancers such as those originated from lung, bladder, and renal tissues. In some cancer types such as colorectal cancer, hepatocellular carcinoma and papillary thyroid carcinoma, there is no agreement about BANCR expression, necessitating the importance of additional functional studies in these tissues. In the present manuscript, we review the investigations related to BANCR expression changes in cancerous cell lines, clinical samples, and animal models of cancer. We also discuss the outcome of its deregulation in cancer progression, prognosis, and the underlying mechanisms of these observations.

Keywords: BANCR; biomarker; cancer; expression; lncRNA.

FIGURE 1

A schematic diagram of the oncogenic role of lncRNA BANCR in regulating Wnt/β-catenin signaling pathway in pancreatic cancer and retinoblastoma. Accumulating research has figured out that lncRNA BANCR could play a crucial role in triggering the activation of Wnt/β-catenin cascade in several tumor cells through sponging various miRNAs. As an illustration, this lncRNA could elevate pancreatic cancer tumorigenesis through up-regulating expression levels of β-catenin, c-Myc, and cyclinD1 by miR-195-5p/Wnt/β-catenin axis in target cells (Wu et al., 2019). In addition, overexpression of lncRNA BANCR through regulating Wnt/β-catenin pathway could promote cell proliferation, apoptosis, invasion, and migration in retinoblastoma. In fact, this lncRNA via sponging miR-204-3p could have an effective part in enhancing the expression levels of Wnt4, β-catenin, and TCF4 in tumor cells (Sun et al., 2020). Green arrows indicate the up-regulation of target genes modulated via lncRNA BANCR and red arrows depict inhibition of miRNAs regulated by this lncRNA.

FIGURE 2

A schematic representation of the potential role of fentanyl as an anti-tumor drug in colorectal cancer cells. Accumulating evidence illustrates that Ets-1 could negatively regulate the expression of BANCR through the deacetylation of histones H3 within BANCR promoter. The regulatory role of fentanyl on reducing the expression level of Ets-1 and inducing BANCR upregulation could have a significant part in decreasing cell clonal formation, as well as cell migration and invasion in colorectal cancer (Li A.-x. et al., 2015). Therefore, lncRNA BANCR could play an effective role as a tumor suppressor in the regulation of colorectal cancer cells (Li A.-x. et al., 2015). Green arrow indicates the regulatory role of fentanyl on the overexpression of lncRNA BANCR, red arrows depict the inhibitory role of fentanyl on the expression of Ets-1, and the impact of Ets-1 on down-regulating the expression level of BANCR.

FIGURE 3

A schematic illustration of tumor suppressive role of lncRNA BANCR in inhibiting proliferation and migration of lung carcinoma through MAPK pathways. LncRNA BANCR via suppressing the activation of p38 MAPK and JNK and modulating MAPK cascades could effectively reduce cell proliferation and migration of lung carcinoma (Jiang et al., 2015). Red arrows illustrate downregulation of target genes modulated via lncRNA BANCR.

FIGURE 4

A schematic diagram of oncogenic role of lncRNA BANCR in modulating the expression of MMP2 and MMP1 via ERK/MAPK cascade in endometrial cancer. LncRNA BANCR could up-regulate in type 1 endometrial cancer tissues, and play an effective role in the progression of this type of tumor. This lncRNA via activating ERK/MAPK signaling pathway could promote the expression levels of MMP2 and MMP1, and thereby suppressing cell proliferation, migration, and invasion of EC cells (Wang D. et al., 2016). Green arrows indicate the up-regulation of target genes modulated via lncRNA BANCR.

FIGURE 5

A schematic summary of the role of BANCR and EZH2 modulation on the expression of cyclin D1. LncRNA BANCR could regulate growth and cell cycle of papillary thyroid carcinoma via the modulation of cyclin D1 protein expression. Furthermore, via physical binding of BANCR to EZH2, this lncRNA could regulate TSHR and the following target genes especially cyclin D1 (Zheng et al., 2016). BANCR has an oncogenic role in the modulation of PTC cancer (Zheng et al., 2016).

FIGURE 6

A schematic illustration of the oncogenic role of BANCR in modulating the RAF/MEK/ERK signaling pathway in papillary thyroid carcinoma. The MAPK-signaling cascade is generally triggered via the activation of a receptor tyrosine kinase that could play an important role in activating RAS, which in turn, facilitates homo- or heterodimerization of wild-type BRAF. Activated BRAF could have a potential role in phosphorylating MEK (which is bound to KSR) that could phosphorylate ERK, and thereby leading to various cellular effects including proliferation and survival. Mutant BRAF could trigger dimerization and activation of MEK without Ras activation (Caronia et al., 2011). Growing evidence has demonstrated that lncRNA BANCR could play a crucial role in enhancing epithelial-mesenchymal transition in papillary thyroid carcinoma via up-regulating the expression levels of CRAF, MEK1/2, and ERK1/2 in tumor cells (Wang et al., 2018a,b). Green arrows indicate the up-regulation of target genes modulated via lncRNA BANCR.