BRAF-activated Non-coding RNA Overexpression Research Articles

A BRAF-activated non-coding RNA attenuates clear cell renal cell carcinoma via repression of glucose-6-phosphate dehydrogenase.

Clear cell renal cell carcinoma (ccRCC) is a disease rooted in metabolic disorders, distinguished by abnormally high activity of glucose 6-phosphate dehydrogenase (G6PD). G6PD serves as a key rate-limiting enzyme in the pentose phosphate pathway. Meanwhile, BRAF-activated non-coding RNA (BANCR) has emerged as a crucial regulatory factor linked to various cancers. The expression pattern of BANCR varies across different cancer types, exhibiting apparent duality in its function. However, the precise role and underlying mechanisms of BANCR in ccRCC tumorigenesis remain incompletely understood. Our study indicated that BANCR was downregulated in ccRCC and influenced cell survival by modulating cell proliferation, apoptosis, and G6PD enzyme activity. The underlying mechanism was that BANCR could directly bind to G6PD through a lncRNA-protein interaction, ultimately inhibiting G6PD activity by impeding its dimer formation. Moreover, BANCR exhibited the capability to modulate the glucose metabolic flow in ccRCC cells. Subsequent experiments demonstrated a significant inhibition of tumor growth in vivo upon overexpression of BANCR, and G6PD played a pivotal role in mediating the tumor suppressive effect of BANCR in ccRCC cells. In conclusion, this study provides novel insights into the molecular pathogenesis of ccRCC, highlights a distinct and new regulatory mechanism responsible for the ectopic overactivation of G6PD in ccRCC progression, and suggests that BANCR-mediated suppression of G6PD activity could emerge as a potential therapeutic strategy for ccRCC treatment.

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.

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.

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.

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.

BRAF-activated LncRNA functions as a tumor suppressor in papillary thyroid cancer.

Long non-coding RNAs (lncRNAs) participate in cancer cell tumorigenesis, cell cycle control, migration, proliferation, apoptosis, metastasis and drug resistance. The BRAF-activated non-coding RNA (BANCR) functions as both an oncogene and a tumor suppressor. Here, we investigated BANCR's role in papillary thyroid carcinoma (PTC) by assessing BANCR levels in PTC and matched normal thyroid epithelial tissues from 92 patients using qRT-PCR. We also used lentiviral vectors to establish PTC cell lines to investigate the effects of BANCR overexpression on cancer cell proliferation, apoptosis, migration and invasion. Our results indicate BANCR levels are lower in PTC tumor tissues than control tissues. Decreased BANCR levels correlate with tumor size, the presence of multifocal lesions and advanced PTC stage. BANCR overexpression reduced PTC cell proliferation and promoted apoptosis, which inhibited metastasis. It also inactivated ERK1/2 and p38, and this effect was enhanced by treatment with the MEK inhibitor U0126. Finally, BANCR overexpression dramatically inhibited tumor growth from PTC cells in xenograft mouse models. These results suggest BANCR inhibits tumorigenesis in PTC and that BANCR levels may be used as a novel prognostic marker.

Increased expression of LncRNA BANCR and its prognostic significance in human hepatocellular carcinoma.

BackgroundLong noncoding RNAs (lncRNAs) have been proved to play important roles in the tumorigenesis and development of human hepatocellular carcinoma (HCC). The aim of our study is to investigate the expression and function of BRAF-activated noncoding RNA (BANCR) in HCC.MethodsBANCR expression was detected in HCC tissues and cell lines by using quantitative real-time PCR (qRT-PCR). Association between BANCR levels and clinicopathological factors and patient prognosis was also analyzed. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), flow cytometry, and transwell invasion and migration assays were used to investigate the role of BANCR in the regulation of biological behaviors of HCC cells.ResultsBANCR expression was remarkably increased in HCC tissues compared with adjacent noncancerous tissues (P < 0.001). BANCR expression in four HCC cell lines was also significantly upregulated (P < 0.05). Clinicopathologic analysis revealed that high BANCR expression correlated with high tumor grade, large tumor size, venous infiltration, advanced tumor, node, and metastasis (TNM) stage, and shorter overall survival. Multivariate regression analysis identified BANCR overexpression as an independent unfavorable prognostic factor (relative risk [RR] 4.245; P = 0.015) in HCC patients. Moreover, BANCR downregulation in Hep3B cells impaired cell proliferation, promoted cell apoptosis, reduced cell invasion and migration, led to downregulated vimentin, and upregulated E-cadherin protein levels.ConclusionsThese findings suggested that BANCR may contribute to HCC initiation and progression and would be used as not only a novel prognostic marker but also a potential therapeutic target for this disease.

Increased expression of the lncRNA BANCR and its prognostic significance in human osteosarcoma.

Long noncoding RNAs (lncRNAs) play important roles in the formation and progression of many types of human malignancies. The aim of our study was to investigate the expression and biological functions of the lncRNA BRAF-activated noncoding RNA (BANCR) in human osteosarcoma. BANCR expression was quantified by real-time PCR in human osteosarcoma cell lines and tissues. We analyzed the association between BANCR levels and clinicopathological factors and patient prognosis. MTT, flow cytometric, and transwell invasion assays were performed to observe the effects of BANCR on MG-63 cell biological behaviors. BANCR overexpression was observed in osteosarcoma cell lines and clinical specimens. Increased BANCR expression was significantly associated with large tumor size, positive distant metastasis, and advanced clinical stage. High BANCR expression in osteosarcoma was an independent predictor of poor survival. Downregulation of BANCR inhibited MG-63 cell proliferation and invasion and promoted cell apoptosis in vitro. These findings suggested that BANCR may act as a tumor promoter in osteosarcoma and could serve as a potential therapeutic target for this disease.

Downregulated Long Noncoding RNA BANCR Promotes the Proliferation of Colorectal Cancer Cells via Downregualtion of p21 Expression.

BRAF activated non-coding RNA (BANCR), a long non-coding RNA (lncRNA), is crucial for cell migration in melanoma cells and non-small cell lung cancer (NSCLC) cells. However, little is known regarding the role of this gene in the proliferation of colorectal cancer. Therefore, we investigated the involvement of BANCR in the proliferation of colorectal cancer cells. In this study, we show that BANCR expression was significantly down-regulated in colorectal cancer tissues compared with normal tissues, and overexpression of BANCR suppressed colorectal cancer cell growth in vitro and in vivo. We also determined that pCDNA-BANCR-mediated colorectal cancer cell proliferation was associated with induction of G0/G1 cell-cycle arrest and apoptosis enhancement through regulation of p21, and its effects were most likely posttranscriptional. Taken together, our findings suggest that down-regulation of BANCR contributes to the proliferation of colorectal cancer cells, at least in part, through the regulation of p21 protein.

Increased expression of LncRNA BANCR is associated with clinical progression and poor prognosis in gastric cancer

Long non-coding RNAs (lncRNAs), emerging non-coding RNAs, have been proved to serve as a critical role in the proliferation, metastasis apoptosis of gastric cancer. However little is known about the clinical significance of BRAF-activated non-coding RNA (BANCR) in gastric cancer. The aim of our study is to identify the clinical value of BANCR in gastric cancer patients. Expression of BANCR was analyzed in one hundred and eighty-four gastric cancer samples using Real-time PCR. In our results, the expression of BANCR was increased in gastric cancer tissues compared with paired adjacent normal tissues. Moreover, high expression of BANCR was positively associated with clinical stage, tumor depth, lymph node metastasis and distant metastasis in gastric cancer patients. In survival analysis, high expression of BANCR was an independent unfavorable prognostic factor in gastric cancer patients. In summary, overexpression of BANCR acts as an unfavorable prognostic biomarker in gastric cancer patients.

Long non-coding RNA BANCR promotes proliferation in malignant melanoma by regulating MAPK pathway activation.

Long non-coding RNAs (lncRNAs) have been shown to be implicated in the complex network of cancer including malignant melanoma and play important roles in tumorigenesis and progression. However, their functions and downstream mechanisms are largely unknown. This study aimed to investigate whether BRAF-activated non-coding RNA (BANCR), a novel and potential regulator of melanoma cell, participates in the proliferation of malignant melanoma and elucidate the underlying mechanism in this process. We found that BANCR was abnormally overexpressed in human malignant melanoma cell lines and tissues, and increased with tumor stages by quantitative PCR. BANCR knockdown induced by shRNA transfection significantly inhibited proliferation of tumor cells and inactivated MAPK pathway, especially by silencing the ERK1/2 and JNK component. Moreover, combination treatment of BANCR knockdown and suppression ERK1/2 or JNK (induced by specific inhibitors U0126 or SP600125 respectively) produced synergistic inhibitory effects in vitro. And the inhibitory effects induced by ERK1/2 or JNK could be rescued by BANCR overexpression. By tumorigenicity assay in BALB/c nude mice, we further found that BANCR knockdown inhibited tumor growth in vivo. In addition, patients with high expression of BANCR had a lower survival rate. Taken together, we confirmed the abnormal upregulation of a novel lncRNA, BANCR, in human malignant melanoma. BANCR was involved in melanoma cell proliferation both in vitro and in vivo. The linkage between BANCR and MAPK pathway may provide a novel interpretation for the mechanism of proliferation regulation in malignant melanoma.

Downregulation of BRAF activated non-coding RNA is associated with poor prognosis for non-small cell lung cancer and promotes metastasis by affecting epithelial-mesenchymal transition

BackgroundRecent evidence indicates that long noncoding RNAs (lncRNAs) play a critical role in the regulation of cellular processes, such as differentiation, proliferation and metastasis. These lncRNAs are found to be dysregulated in a variety of cancers. BRAF activated non-coding RNA (BANCR) is a 693-bp transcript on chromosome 9 with a potential functional role in melanoma cell migration. The clinical significance of BANCR, and its’ molecular mechanisms controlling cancer cell migration and metastasis are unclear.MethodsExpression of BANCR was analyzed in 113 non-small cell lung cancer (NSCLC) tissues and seven NSCLC cell lines using quantitative polymerase chain reaction (qPCR) assays. Gain and loss of function approaches were used to investigate the biological role of BANCR in NSCLC cells. The effects of BANCR on cell viability were evaluated by MTT and colony formation assays. Apoptosis was evaluated by Hoechst staining and flow cytometry. Nude mice were used to examine the effects of BANCR on tumor cell metastasis in vivo. Protein levels of BANCR targets were determined by western blotting and fluorescent immunohistochemistry.ResultsBANCR expression was significantly decreased in 113 NSCLC tumor tissues compared with normal tissues. Additionally, reduced BANCR expression was associated with larger tumor size, advanced pathological stage, metastasis distance, and shorter overall survival of NSCLC patients. Reduced BANCR expression was found to be an independent prognostic factor for NSCLC. Histone deacetylation was involved in the downregulation of BANCR in NSCLC cells. Ectopic expression of BANCR impaired cell viability and invasion, leading to the inhibition of metastasis in vitro and in vivo. However, knockdown of BANCR expression promoted cell migration and invasion in vitro. Overexpression of BANCR was found to play a key role in epithelial-mesenchymal transition (EMT) through the regulation of E-cadherin, N-cadherin and Vimentin expression.ConclusionWe determined that BANCR actively functions as a regulator of EMT during NSCLC metastasis, suggesting that BANCR could be a biomarker for poor prognosis of NSCLC.

Persistent Vertigo

Long non-coding RNAs (lncRNAs), emerging non-coding RNAs, have been proved to serve as a critical role in the proliferation, metastasis apoptosis of gastric cancer. However little is known about the clinical significance of BRAF-activated non-coding RNA (BANCR) in gastric cancer. The aim of our study is to identify the clinical value of BANCR in gastric cancer patients. Expression of BANCR was analyzed in one hundred and eighty-four gastric cancer samples using Real-time PCR. In our results, the expression of BANCR was increased in gastric cancer tissues compared with paired adjacent normal tissues. Moreover, high expression of BANCR was positively associated with clinical stage, tumor depth, lymph node metastasis and distant metastasis in gastric cancer patients. In survival analysis, high expression of BANCR was an independent unfavorable prognostic factor in gastric cancer patients. In summary, overexpression of BANCR acts as an unfavorable prognostic biomarker in gastric cancer patients.