BRAF-activated Non-coding RNA Research Articles

Interaction of BANCR in the relationship between Hashimoto's thyroiditis and papillary thyroid carcinoma expression patterns and possible molecular mechanisms.

Previous studies have established a connection between Hashimoto's thyroiditis (HT) and an increased risk of papillary thyroid carcinoma (PTC). However, the molecular mechanisms driving this association are not well understood. The long non-coding RNA (lncRNA) BRAF-activated non-coding RNA (BANCR) has been implicated in various cancers, suggesting a potential role in the HT-PTC linkage. This study investigated the expression levels of BANCR in PTC and HT samples, compared to control tissues. We also examined the association between BANCR expression and clinicopathological features, including lymph node metastasis. Furthermore, we explored the molecular mechanisms of BANCR in PTC pathogenesis and its potential as a therapeutic target. BANCR expression was significantly lower in PTC samples than in controls, while it was moderately increased in HT samples. In PTC cases with concurrent HT, BANCR expression was markedly reduced compared to normal tissues. Our analysis revealed BANCR's role as an oncogene in PTC, influencing various cancer-related signaling pathways. Interestingly, no significant correlation was found between BANCR expression and lymph node metastasis. Our findings underscore the involvement of BANCR in the connection between HT and PTC. The distinct expression patterns of BANCR in PTC and HT, especially in PTC with concurrent HT, provide new insights into the molecular interplay between these conditions. This study opens avenues for the development of innovative diagnostic and therapeutic strategies targeting BANCR in PTC and HT.

STM2457 Inhibits the Invasion and Metastasis of Pancreatic Cancer by Down-Regulating BRAF-Activated Noncoding RNA N6-Methyladenosine Modification.

Pancreatic cancer is a malignant tumor of the digestive system that is highly malignant, difficult to treat, and confers a poor prognosis for patients. BRAF-activated noncoding RNA (BANCR) has been proven to play an important role in the invasion and metastasis of pancreatic cancer. In this study, we focused on BANCR as a potential therapeutic target for human pancreatic cancer. The BANCR level in pancreatic cancer tissues and cells is affected by m6A methylation. Based on this, the aim of our study was to investigate the effect of a highly potent and selective first-in-class catalytic inhibitor of METTL3 (STM2457) on BANCR m6A methylation and its malignant biological behaviors in pancreatic cancer. The relationship between BANCR expression and BANCR m6A modification was detected with RT-qPCR and MeRIP-PCR. The expression of methyltransferase-like 3 (METTL3), the key enzyme involved in m6A methylation, in pancreatic cancer tissues was detected using a Western blot. STM2457 was used in vitro to investigate its resistance to the proliferation, invasion, and metastasis of pancreatic cancer cells. BANCR was overexpressed in pancreatic cancer tissues and cells, which was associated with poor clinical outcomes and validated in pancreatic cancer cell lines. m6A modification was highly enriched within BANCR and enhanced its expression. Remarkably, STM2457 inhibited the proliferation, invasion, and metastasis of pancreatic cancer cells by down-regulating BANCR m6A modifications. This study demonstrates the promise of BANCR as a new diagnostic and therapeutic target for pancreatic cancer and reveals the therapeutic effect that STM2457 exerts on pancreatic cancer by down-regulating BANCR m6A modifications.

Study of LncRNA BANCR Expression in Tumor Tissues and Adjacent Normal Tissues in Gastric Cancer Patients.

Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in various biological processes, including cancer development and progression. This study aimed to investigate the expression differences of the BRAF-activated non-coding RNA (BANCR) gene in GC tissues compared to adjacent normal tissues. The potential diagnostic significance of BANCR in GC was explored, with the aim of improving diagnostic and therapeutic approaches for this global health burden. Tissue samples from 100 gastric cancer (GC) patients were collected, and BANCR expression was analyzed using quantitative real-time PCR. Correlations between BANCR expression and clinicopathological features were assessed, and its biomarker potential was evaluated. In individuals diagnosed with GC, the expression of BANCR was notably elevated in tumor tissues compared to adjacent normal tissues (P < 0.0001). However, the analysis of gene expression data did not demonstrate any statistically significant correlation between elevated BANCR expression and clinicopathological features. According to the ROC analysis, BANCR demonstrated an AUC of 0.6733 (P < 0.0001), with a sensitivity of 73% and a specificity of 45%. However, further evaluation is required to determine its potential as a biomarker (CI 95% = 0.5992 to 0.7473). The observed upregulation of BANCR in GC tissues implies its potential involvement as an oncogenic lncRNA in GC patients. Furthermore, BANCR may serve as a promising biomarker for identification and treatment of GC.

Systematic Survey of the Regulatory Networks of the Long Noncoding RNA BANCR in Cervical Cancer Cells.

Long noncoding RNAs (lncRNAs) are increasingly recognized as functional regulators of human cancers. BRAF-activated noncoding RNA (BANCR), an oncogenic lncRNA, has a carcinogenic effect on many types of cancers. However, the clinical significance and molecular mechanisms of BANCR in cervical cancer are still unclear. Here, we generated BANCR knockout cell lines via CRISPR/Cas9 editing and revealed that BANCR plays roles in the apoptosis, proliferation, and migration of HeLa cells. A quantitative proteomics strategy was employed to globally identify BANCR-regulated proteins in HeLa cells. In total, we identified 569 differentially expressed proteins (DEPs) upon knockout of BANCR in HeLa cells. Bioinformatic analysis revealed that these DEPs were involved in diverse cellular pathways. Functional studies revealed that BANCR exerts its effects on the proliferation and apoptosis of HeLa cells through the regulation of cAMP-responsive element binding protein 1 (CREB1) expression. Mechanistically, BANCR could inhibit the expression of miR-582-5p, and CREB1 is a direct target of miR-582-5p; therefore, BANCR may exert its function by regulating CREB1 expression via targeting miR-582-5p in cervical cancer cells. Collectively, this study established a proteome-wide BANCR regulatory network, which provides novel insight into the molecular pathogenesis of cervical cancer and can serve as a basis for the development of targeted therapies.

Long non‑coding RNA BANCR promotes proliferation, invasion and migration in esophageal squamous cell carcinoma cells via the Raf/MEK/ERK signaling pathway.

Esophageal squamous cell carcinoma (ESCC) is a major histological type of esophageal cancer, identified as a leading cause of tumor-associated death worldwide. In addition, long non-coding RNA (lncRNA) BRAF-activated non-coding RNA (BANCR) expression is increased in the plasma of patients with ESCC, which can be reversed by tumor resection. Thus, the aim of the present study was to investigate the underlying mechanism of BANCR in ESCC progression. The relative mRNA expression of BANCR was determined via reverse transcription-quantitative PCR. The cell behaviors of Eca-109 cells were detected using Cell Counting Kit-8, colony formation, wound healing and Transwell chamber assays. Finally, the expression levels of proteins involved in the Raf/MEK/ERK signaling pathway and cell metastasis were analyzed with western blotting. The results revealed that lncRNA BANCR was highly expressed in ESCC cells compared with in normal esophageal cells. BANCR overexpression enhanced proliferation, migration and invasion of ESCC cells, and BANCR silencing exerted opposite effects. Moreover, BANCR overexpression induced activation of the Raf/MEK/ERK signaling pathway in ESCC cells. Notably, U0126, a specific MEK inhibitor, decreased MEK and ERK expression, and blocked the promotive effects of BANCR overexpression on the proliferation, migration and invasion of ESCC cells. Overall, lncRNA BANCR facilitated the proliferation, migration and invasion of ESCC cells via the Raf/MEK/ERK signaling pathway. Thus, lncRNA BANCR may be a promising target for inhibiting ESCC growth and metastasis.

LncRNA BANCR Attenuates the Killing Capacity of Cisplatin on Gastric Cancer Cell Through the ERK1/2 Pathway.

PurposeChemotherapy-based comprehensive treatments are the most important therapeutic methods for patients with advanced gastric cancer, but chemoresistance often cause treatment failure. Long non-coding RNA (LncRNA) BRAF-activated non-coding RNA (BANCR) has been shown to participate in many biological behaviors of multiple cancers. However, the biological roles of LncRNA BANCR in chemoresistance of gastric cancer remain unclear. Here, we aimed to evaluate the functions of LncRNA BANCR on the therapy of gastric cancer.MethodsIn this study, LncRNA BANCR expression was detected in gastric cancer patient samples and cell lines by quantity polymerase chain reaction (qPCR). Cell proliferation and viability in cisplatin-treated cells were measured using clonogenic survival assay and cell counting kit-8. The levels of ERK1/2 pathway molecules were tested with Western blot. Ly3214996, an inhibitor of ERK signal pathway, was administered to assess the effects of BANCR overexpression on gastric cancer cell with cisplatin-treated resistance. Moreover, the role of BANCR in cisplatin resistance of gastric cancer was validated in xenograft mouse models in vivo.ResultsOur study revealed that LncRNA BANCR expression was also significantly increased in gastric cancer tissues compared with adjacent normal tissues. Furthermore, we found that BANCR overexpression promoted gastric cancer cell resistance to cisplatin in vitro. Ly3214996 treatment abolished the BANCR overexpression-mediated gastric cancer cell cisplatin resistance via regulating the phosphorylation of ERK protein. Knock-down of BANCR significantly delayed tumor growth in xenograft mouse models.ConclusionBANCR promoted cisplatin resistance of gastric cancer cells by activating ERK1/2 pathway. Inhibition of BANCR markedly suppressed the growth of gastric cancer cells in vitro as well as in vivo. These results provided a new strategy for gastric cancer therapy via targeting BANCR.

LncRNA BANCR induced vascular smooth muscle cell proliferation by downregulating miR-34c methylation in atherosclerosis.

Aberrant vascular smooth muscle cell (VSMCs) proliferation involves in the development of atherosclerosis. It reported that Long noncoding BRAF-activated noncoding RNA (BANCR) and miR-34c played opposite roles in the regulation of the proliferation of VSMCs, indicating that there might be a potential interaction between them. This study was to investigate the relationship between BANCR and miR-34c in atherosclerosis. Blood (5ml) was obtained from 56 patients with atherosclerosis and 56 healthy volunteers after they were fasted overnight, and plasma was extracted from the blood. Human Aortic Smooth Muscle Cells (HASMCs) were used to perform in vitro cell experiments. RT-qPCR was performed to measure the expression of BANCR and miR-34c in plasma and HASMCs. Dual luciferase reporter assay detected the interaction between BANCR and miR-34c. CCK-8 assay was used to assess the effects of BANCR and miR-34c overexpression on the proliferation of HASMCs. Western blotting was used to assess the effects of BANCR and miR-34c overexpression on the protein expression of HMGB1, TNF-ɑ and Bcl-2. In this study, we found that BANCR was upregulated, while miR-34c was downregulated in atherosclerosis. Bioinformatics analysis showed that BANCR and miR-34c could directly interact with each other. Moreover, overexpression of BANCR could decrease the expression of miR-34c in HASMCs, but overexpression of miR-34c could not affect the expression of BANCR. Furthermore, overexpression of BACNR increased miR-34c methylation, and knockdown of endogenous BANCR decreased miR-34c methylation. In addition, overexpression of BANCR reduced the effects of miR-34c on HASMCs proliferation and reversed the effects of miR-34c on HMGB1, TNF-ɑ and Bcl-2 expression. BANCR overexpression could induce HASMCs proliferation by downregulating the miR-34c methylation. Therefore given BANCR upregulation in atherosclerosis, its expression may be considered as a novel and useful biomarker for atherosclerosis prevention and prognosis. However considering the possible effects of other underlying diseases on both BANCR expression and miR-34c in atherosclerosis, further investigation is suggested for future research.

Long non‑coding RNA BANCR mediates esophageal squamous cell carcinoma progression by regulating theIGF1R/Raf/MEK/ERK pathway via miR‑338‑3p.

Esophageal squamous cell carcinoma (ESCC) is a type of digestive tract malignant tumor that severely threatens human health. The long non-coding RNA BRAF activated non-coding RNA (BANCR) and insulin-like growth factor 1 receptor (IGF1R) are associated with various types of cancer; however, it remains unclear whether BANCR can regulate IGF1R expression in ESCC. In the present study, the expression levels of BANCR, IGF1R mRNA and microRNA-338-3p (miRNA/miR-338-3p) in ESCC tissues or cells were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The levels of IGF1R, E-cadherin, N-cadherin, Vimentin, p-Raf-1, p-MEK1/2 and p-ERK1/2 were measured by western blot analysis. The proliferation, migration and invasion of ESCC cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zolium bromide (MTT) or Transwell assays. The relationship between miR-338-3p and BANCR or IGF1R was predicted using starBase2.0 and confirmed by dual-luciferase reporter assay. The role of BANCR in ESCC in vivo was confirmed through a tumor xenograft assay. It was found that BANCR and IGF1R were upregulated, while miR-338-3p was down-regulated in ESCC tissues and cells. Both BANCR and IGF1R knockdown suppressed the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of ESCC cells. IGF1R enhancement reversed BANCR knockdown-mediated effects on the proliferation, migration, invasion and EMT of ESCC cells. BANCR regulated the Raf/MEK/ERK pathway by regulating IGF1R expression. Notably, BANCR regulated IGF1R expression by sponging miR-338-3p. Moreover, BANCR silencing inhibited tumor growth in vivo. On the whole, the findings of the present study demonstrate that BANCR inhibition blocks ESCC progression by inactivating the IGF1R/Raf/MEK/ERK pathway by sponging miR-338-3p.

BRAFV600E mutation, BRAF-activated long non-coding RNA and miR-9 expression in papillary thyroid carcinoma, and their association with clinicopathological features

BackgroundThe incidence of thyroid cancer is increasing worldwide. This study investigated the association of B-type RAF kinase (BRAF)V600E mutation status, the expression of BRAF-activated long non-coding RNA (BANCR) and microRNA miR-9, and the clinicopathological features of papillary thyroid carcinoma (PTC).MethodsClinicopathological data for PTC patients (n = 51) diagnosed and treated between 2018 and 2019 were collected. Carcinoma and adjacent normal tissue samples were analyzed for the presence of the BRAFV600E mutation and/or expression of BANCR and miR-9.ResultsLarger tumor, higher rate of bilateral tumors and multifocality, extracapsular invasion, and lateral lymph node metastasis (LNM) were observed in PTC patients with BRAF V600E mutation. Patients with higher BANCR expression had a higher rate of extracapsular invasion and lateral LNM in carcinoma tissue and a lower frequency of bilateral tumors and multifocality in normal adjacent tissue. Patients with higher miR-9 expression had a lower rate of central and lateral LNM in carcinoma tissue and higher rates of bilateral tumor location and multifocality in normal adjacent tissue. Patients with BRAFV600E mutation have a higher rate of BANCR overexpression and tended to have a lower rate of miR-9 overexpression (P = 0.057), and a negative association was observed between BANCR and miR-9 expression in carcinoma tissue.ConclusionsBRAFV600E mutation and the BANCR and miR-9 expression were closely associated with the tumor size, bilateral tumor location, multifocality, extracapsular invasion, and lateral LNM. PTC patients with these clinicopathological characteristics, BRAFV600E mutation, and high BANCR expression and low miR-9 expression needed earlier surgical treatment and are recommended for total thyroidectomy in primary surgery for reducing the risk of recurrence. These findings provide new insight into the molecular basis for PTC and can inform strategies for the management of PTC.

Effects of lncRNA BANCR on endometriosis through ERK/MAPK pathway.

To investigate the regulatory role of long non-coding ribonucleic acid (lncRNA) BRAF-activated non-coding RNA (BANCR) in rats with endometriosis (EMs) and its mechanism of action. A total of 30 healthy, unmated, female Sprague-Dawley (SD) rats were selected and divided into sham-operation group, model group and lncRNA BANCR intervention group, and a rat model of EMs was established by means of autotransplantation. The volume of eutopic endometrium in each group of rats was measured, and hematoxylin and eosin (HE) staining was applied to detect the impacts on the pathological morphology of ectopic endometrial tissues in each group. The levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and MMP-9 in the rat serum were determined by virtue of enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR) was performed to measure the messenger RNA (mRNA) levels of extracellular signal-regulated kinase (ERK) and mitogen-activated protein kinase (MAPK) in the uterine tissues in each group of rats, and Western blotting assay was adopted to detect the levels of phosphorylated ERK and MAPK proteins in the rat uterine tissues in each group. Compared with those in sham-operation group, the volume of eutopic endometrium in the rats was increased markedly, the pathological morphology was poorer, and the content of VEGF, MMP-2 and MMP-9 in the serum, the mRNA levels of ERK and MAPK in the uterine tissues, and the levels of phosphorylated ERK and MAPK proteins were elevated notably in model group. The rats in lncRNA BANCR intervention group had evidently decreased volume of eutopic endometrium, improved pathological morphology and significantly declined content of serum VEGF, MMP-2 and MMP-9, ERK and MAPK mRNA levels, and phosphorylated ERK and MAPK protein levels in the uterine tissues than those in model group. LncRNA BANCR inhibitor can repress the development of ectopic endometrial tissues by inhibiting the generation of angiogenic factors in the EMs focus, and its mechanism may be related to the inhibition on the ERK/MAPK signaling pathway.

LncRNA LINC-PINT is downregulated in melanoma and regulates cell proliferation by downregulating lncRNA BANCR.

The development of melanoma may involve long non-coding RNAs (lncRNAs); however, the functions of the majority of lncRNAs in melanoma are unknown. The present study investigated the role of long intergenic non-protein coding RNA p53 induced transcript (LINC-PINT) in melanoma. In the present study, quantitative PCR was used to detect gene expression, overexpression experiments were performed to analyze gene interactions and CCK-8 assays were used to analyze cell proliferation. LINC-PINT was downregulated, while BRAF-activated non-coding RNA (BANCR) was upregulated in melanoma tissues compared with normal adjacent tissues. Expression levels of LINC-PINT decreased, while expression levels of BANCR increased with increasing tumor thickness. The expression levels of LINC-PINT and BANCR were inversely associated in melanoma tissues but not in healthy adjacent tissue. LINC-PINT overexpression downregulated BANCR expression in melanoma cells, while BANCR overexpression did not significantly affect LINC-PINT expression. LINC-PINT overexpression inhibited melanoma cell proliferation in vitro compared to controls. BANCR overexpression attenuated the effects of LINC-PINT overexpression. The present study revealed that lncRNA LINC-PINT is downregulated in melanoma and may regulate melanoma cell proliferation by downregulating lncRNA BANCR.

Proinflammatory cytokine IFN-γ, lncRNA BANCR and the occurrence of coronary artery disease

AimsCoronary artery disease (CAD) ranks the leading cause of death globally. Interferon-γ (IFN-γ) gene, along with long noncoding RNA (lncRNA) BRAF-activated noncoding RNA (BANCR), could coordinately function in the occurrence of CAD. We hypothesized that level of IFN-γ, genetic variants of IFN-γ and BANCR gene should be associated with the occurrence of CAD. Materials and MethodsA case-control study was conducted in Chinese population. Key findingsWe found that serum level of IFN-γ in CAD cases was significantly higher than that in controls (P < 0.001). Compared with the first quartile, all of the second (OR: 1.87; 95% CIs: 1.33–2.62), the third (OR: 1.79; 95% CIs: 1.30–2.45), and the fourth (OR: 3.98; 95% CIs: 2.59–6.12) quartiles of serum level of IFN-γ were associated with increased risk of CAD (P < 0.05). We found IFN-γ gene (rs2069705 and rs2430561), and 2 variants in lncRNA BANCR (rs6559446 and rs79823312) could increase CAD susceptibility in allelic and dominant model, while IFN-γ rs2069705 and rs2430561, BANCR rs79823312 were also associated with CAD risk in additive model. IFN-γ rs2069705 and rs2430561 were associated with higher level of serum IFN-γ in CAD patients (P < 0.001). SignificanceThis study confirmed the crucial role of IFN-γ and lncRNA BANCR in the occurrence of CAD, and might serve as the biomarkers of CAD screening and prevention.

LncRNA BANCR suppresses cell viability and invasion and promotes apoptosis in non-small-cell lung cancer cells in vitro and in vivo.

Background: As a leading cause of deaths worldwide, lung cancer is a collection of diseases with diverse etiologies which includes non-small-cell lung cancer (NSCLC). Increasing evidence reported that aberrant expression of BRAF activated non-coding RNA (BANCR) was involved in the tumorigenesis and progression of various malignancies.Purpose and methods: However, its role in NSCLC has not been completely clarified. In the present study, we identified the role of BANCR in the regulation of NSCLC cell viability, invasion, and apoptosis. Down-regulation of BANCR expression was significantly observed in different NSCLC cell lines (A549, H1299, H1650, H1975, SPC-A1, and PC-9), tumor tissue from NSCLC mouse model and 30 human NSCLC tissues compared with adjacent normal tissues.Result: Overexpression of BANCR in these six NSCLC cell lines attenuated the cell viability and invasion. An increased apoptotic level caused by BANCR overexpression was also detected and displayed a conversed influence on Bcl-2 and Bax expression in mRNA and protein level. Furthermore, we identified the effect of BANCR overexpression on tumor growth in NSCLC mouse model. The restoration of BANCR expression inhibits NSCLC.Conclusion: Taken together, our findings shed an insight on the novel molecular mechanisms of lung NSCLC oncogenesis and provide the information for new therapeutic approaches on the disease.

LncRNA BANCR Promotes Pancreatic Cancer Tumorigenesis via Modulating MiR-195-5p/Wnt/β-Catenin Signaling Pathway.

Long noncoding BRAF-activated noncoding RNA has been reported to be tightly associated with tumorigenesis and development in various types of cancers. However, the expression, biological function, and modulatory mechanism of BRAF-activated noncoding RNA in pancreatic cancer remained unclear. In the present work, we explored the carcinogenic activity and underlying mechanism of BRAF-activated noncoding RNA on pancreatic cancer in vitro. We identified that BRAF-activated noncoding RNA was upregulated in pancreatic cancer tissues and cell lines, and BRAF-activated noncoding RNA was related to tumor metastasis and stage. BRAF-activated noncoding RNA reinforces proliferation, invasion, and migration in PANC-1 and SW1990 cells. Moreover, miR-195-5p was downregulated in both PC tissues and cell lines. Our results based on luciferase reporter, RIP-Ago2 and qRT-PCR assays, showed that miR-195-5p was a direct target of BRAF-activated noncoding RNA. Furthermore, miR-195-5p inhibitor abrogated the effects of short-interfering BRAF-activated noncoding RNA on PANC-1 and SW1990 cell growth and invasion in vitro. We further identified that BRAF-activated noncoding RNA played a vital role in activating the Wnt/β-catenin pathway by sponging miR-195-5p. Collectively, our study showed that BRAF-activated noncoding RNA promotes pancreatic cancer tumorigenesis through miR-195-5p/Wnt/β-catenin axis may serve as a potential target for diagnostics and therapeutics in pancreatic cancer.

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

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.

LncRNA BANCR promotes tumorigenesis and enhances adriamycin resistance in colorectal cancer.

Colorectal cancer (CRC) is the third most common malignancy in the United States. Chemotherapeutic resistance is a massive obstacle for cancer treatment. The roles and molecular basis of long non-coding RNA BRAF-activated noncoding RNA (BANCR) in CRC progression and adriamycin (ADR) resistance have not been extensively identified. In this study, we found that BANCR and CSE1L expressions were upregulated in CRC tumor tissues. Meanwhile, CSE1L expression was correlated with depth of CRC. BANCR silencing suppressed cell proliferation and invasion capacity, increased apoptotic rate and potentiated cell sensitivity to ADR. CSE1L downregulation triggered a reduction of cell proliferation and invasion ability, and an increase of apoptosis rate and cell sensitivity to ADR. CSE1L overexpression attenuated si-BANCR-mediated anti-proliferation, anti-invasion and pro-apoptosis effects in CRC cells. BANCR acted as a molecular sponge of miR-203 to sequester miR-203 away from CSE1L in CRC cells, resulting in the upregulation of CSE1L expression. CSE1L knockdown inhibited expressions of DNA-repair-related proteins (53BP1 and FEN1) in HCT116 cells. BANCR knockdown also inhibited tumor growth and enhanced ADR sensitivity in CRC mice model. In conclusion, BANCR knockdown suppressed CRC progression and strengthened chemosensitization of CRC cells to ADR possibly by regulating miR-203/CSE1L axis, indicating that BANCR might be a promising target for CRC treatment.

Long non-coding RNA BANCR regulates cancer stem cell markers in papillary thyroid cancer via the RAF/MEK/ERK signaling pathway

Thyroid cancer is one of the most common malignant tumors of the endocrine system. Among all thyroid cancers, papillary thyroid carcinoma (PTC) is the most common type. The BRAF-activated non-coding RNA (BANCR) is a 693-bp nucleotide transcript which was first identified in melanoma. However, the role of BANCR in the development of thyroid cancer remains unclear. Therefore, the present study investigated the potential involvement of BANCR in the development of thyroid cancer invitro using patient tissue samples and a panel of thyroid cancer cell lines, and invivo using a xenograft mouse model. We observed that BANCR was expressed at a higher level in human thyroid tumor tissues than that noted in the adjacent normal tissues. The expression level of BANCR differed between cultured thyroid cancer cell lines; BANCR expression was lower in the BCPAP cell line than that observed in the CAL-62, WRO and FTC-133 cell lines. Western blot analysis and flow cytometry revealed that overexpression of BANCR in the BCPAP cell line resulted in increased expression of the cancer stem cell markers, LGR5 and EpCAM. Single-clone formation experiments showed that upregulated expression of BANCR in the BCPAP cell line promoted an increase in the number of clones formed. Similarly, in microsphere formation experiments, overexpression of BANCR resulted in increased number and size of microspheres compared with the control cell line. Western blotting experiments showed that BANCR overexpression in BCPAP upregulated the expression of phosphorylated c-Raf, MEK1/2 and ERK1/2. Inhibition of c-Raf via U0126 decreased the expression of LGR5 and EpCAM, as well as phosphorylated levels of c-Raf, MEK1/2 and ERK1/2 in the BCPAP cells, compared to levels in the DMSO controls. In the xenograft mouse model, BANCR overexpression in the thyroid cancer cells significantly increased tumor growth. Taken together, these results suggest that BANCR plays a role in PTC development by regulating the expression of cancer stem cell markers LGR5 and EpCAM via the c-Raf/MEK/ERK signaling pathway. Therefore, BANCR may be used as a novel prognostic marker for PTC.

Long non-coding RNA BANCR indicates poor prognosis for breast cancer and promotes cell proliferation and invasion.

We investigated the expression of human long non-coding ribonucleic acid (lncRNA), BRAF-activated non-coding RNA (BANCR) in breast cancer tissues and its effects on the in vitro proliferation, apoptosis, invasion and metastasis of breast cancer cells; also, we investigated its possible mechanism. The expressions of BANCR in 65 pairs of breast cancer tissues and para-carcinoma normal breast tissues were detected by Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). The expressions of BANCR in normal breast epithelial cells (MCF10A) and breast cancer cells (MCF-7, MDA-MB-231, SKBR3 and BT-20) were further detected. The knockdown efficiency of BANCR small interfering RNA (siRNA) in MCF-7 cells was detected by qRT-PCR. The effects of BANCR knockdown on proliferation, apoptosis, invasion and metastasis capacities of MCF-7 cells were explored via methyl thiazolyl tetrazolium (MTT) proliferation assay, cell colony formation assay, fluorescence-activated cell sorting (FACS) and transwell migration assay. Western blotting was used to detect the changes in expressions of apoptosis-related proteins, epithelial-mesenchymal transition (EMT)-related proteins and matrix metalloproteinases (MMPs) after knockdown of BANCR. The expression level of lncRNA BANCR in breast cancer tissues was significantly higher than that in para-carcinoma normal tissues. The prognosis of patients in low-expression BANCR group was significantly superior to that of patients in high-expression BANCR group. After BANCR knockdown in breast cancer MCF-7 cells, the cell proliferation and colony formation capacities were significantly inhibited. Further mechanism research showed that inhibiting BANCR could promote the apoptosis of MCF-7 cells. Results of Western blotting revealed that the expressions of B-cell lymphoma 2 associated X protein (BAX), cleaved-Caspase-3 and cleaved-poly adenosine diphosphate-ribose polymerase (PARP) in knockdown group were significantly up-regulated compared with those in control group. Both wound-healing assay and transwell migration assay showed that the down-regulation of lncRNA BANCR could inhibit the invasion and metastasis capacities of MCF-7 cells, whose mechanism was related to the inhibition of EMT process and down-regulation of MMP expressions in cells. LncRNA BANCR is highly expressed in breast cancer, which is significantly correlated with the prognosis of patients; moreover, it can promote the growth, invasion and metastasis of ovarian cancer cells. The down-regulation of BANCR can inhibit the proliferation, invasion and metastasis capacities of MCF-7 cells.

The BRAF activated non-coding RNA: A pivotal long non-coding RNA in human malignancies.

Long non-coding RNAs (lncRNAs) participate in the complex network of cancer and play an important role in tumourigenesis and progression. BRAF activated non-coding RNA (BANCR), a 4-exon transcript of 693-bp, was first discovered as an oncogeniclong non-coding RNA in BRAFV600E melanomas cells in 2012 and was related to melanoma cell migration. Besides melanoma, increasing evidence has explored the potential role of BANCR in the development and progression of multiple other human malignancies, such as retinoblastoma, lung cancer, gastric cancer etc. since its discovery. The expression pattern of BANCR varies in different types of cancers, either as a tumour suppressor or as an accelerator. Functional BANCR may serve as a promising biomarker for cancer diagnosis as well as prognosis evaluation. BANCR-targeted intervention may also become a valuable novel therapeutic tool against human malignancies. This review summarized the advanced research progresses concerning the expression and role of BANCR in different human malignancies.

Ultrasound reverses adriamycin-resistance in non-small cell lung cancer via positive regulation of BRAF-activated non-coding RNA (BANCR) expression

Objectives: Multi-drug resistance (MDR) remains one of the major obstacles to successful chemotherapy in patients with cancer. BRAF-activated non-coding RNA (BANCR) has been reported to be regulated in non-small cell lung cancer (NSCLC). In the present study, the researchers investigated the effects of ultrasound on BANCR expression, and its possible mechanisms were investigated in vitro and in vivo. Methods: The Adriamycin-resistance of A549/ADM cells and the transplantation tumor model of A549/ADM in nude mice were established. Real-time PCR was used to quantify BANCR expression in cells and in mice examined with or without ultrasound. P-gp and MRP protein expression were measured by western blot. The cell viability was detected by MTT assay. Results: ANCR expression was significantly elevated by ultrasound in A549/ADM cells and tumor tissue from xenograft mice. In in vitro experiments, P-gp and MRP levels were markedly reduced by ultrasound. When the cancer cells up-regulated BANCR by transfection of pCDNA-BANCR, P-gp and MRP levels were inhibited. In addition, the down-regulation of BANCR by si-BANCR transfection elevated their expression. Conclusion: Ultrasound reversed adriamycin-resistance in A549/ADM cells by regulating BANCR expression, and P-gp and MRP regulation were involved in this process.