Bladder Cancer Associated Transcript 1 Research Articles

Unlocking the Therapeutic Potential of LncRNA BLACAT1 in Hypopharynx Squamous Cell Carcinoma.

Identifying the key molecular targets in hypopharynx squamous cell carcinoma (HSCC) is crucial for understanding this prevalent and highly fatal type of head and neck tumor. The study aims to enhance comprehension of the HSCC process by accurately identifying these key molecular targets. In this study, we examined 47 clinical tissue samples from individuals diagnosed with HSCC using RNA-seq high-throughput assay. Quantitative real-time PCR (RT-PCR) was used to compare long non-coding RNA (lncRNA) bladder cancer-associated transcript 1 (BLACAT1) expression in HSCC tissues versus adjacent non-tumor tissues. The influence of highly expressed lncRNA BLACAT1 on prognostic survival was assessed. Subsequently, we cultured human pharynx squamous cell carcinoma FaDu cells. After reducing lncRNA BLACAT1 expression, we assessed FaDu cell proliferation, invasion, and migration using Cell Counting kit-8 (CCK-8) assay, colony formation assay, EUD assay, Transwell assay, and scratch assay. Additionally, liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS) and western blotting analysis were used to analyze proteins that bind to lncRNA BLACAT1. During in vivo experiments, mice received subcutaneous injections of FaDu cells transfected with lncRNA BLACAT1 shRNA or Scr plasmid (Control) in the dorsal region to observe and compare tumor growth. Lastly, tumor tissues underwent hematoxylin-eosin (HE) and immunohistochemical (IHC) staining. lncRNA BLACAT1 was screened as one of the most significant genes among the group of differentially expressed lncRNAs. RT-PCR exhibited elevated lncRNA BLACAT1 expression in HSCC tissues when compared to non-tumor tissues (p < 0.001). Furthermore, increased lncRNA BLACAT1 expression correlated with advanced clinical stages, heightened lymphatic invasion, and a poor prognosis. Subsequent in vitro experiments solidified our observations, demonstrating lncRNA BLACAT1's promotion of HSCC cell proliferation (p < 0.05), migration (p < 0.01), and invasion (p < 0.01) compared with the control group. Moreover, LC-MS/MS identified signal transducer and activator of transcription 3 (STAT3) and Prohibitin 2 (PHB2) as lncRNA BLACAT1-binding proteins and sh-lncRNA BLACAT1 inhibits STAT3/AKT phosphorylation (p < 0.01) and alters the subcellular distribution of PHB2 and P21 compared with the control group (p < 0.01). Moreover, in vivo experiments showed that lncRNA BLACAT1 inhibition suppresses tumorigenicity in an HSCC xenograft model compared to the control group (p < 0.01). lncRNA BLACAT1 is highly expressed in HSCC tumor tissues and plays a crucial role in the development of HSCC in vitro and in vivo. This increased expression may be caused by STAT3/AKT pathway activation, consequently inhibiting P21 expression through PHB2.

Pathogenesis of psoriasis via miR-149-5p/AKT1axis by long noncoding RNA BLACAT1.

Psoriasis is a chronic, complicated, and recurrent inflammatory skin disease, whose precise molecular mechanisms need to be further explored. The lncRNA bladder cancer-associated transcript 1 (BLACAT1) is aberrantly expressed in many cancers and associated with cellular hyperproliferation and may play a role in the pathogenesis of psoriasis. Thus, this study aimed at identifying the primary mechanism associated with BLACAT1 in psoriasis pathogenesis. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to detect the expression of BLACAT1 in psoriasis tissues. Cell proliferation and apoptosis were assessed using cell counting kit-8 and apoptosis assays, respectively. In vivo experiments and histopathological examinations were performed to investigate the effects of BLACAT1 on psoriasis. Dual-luciferase Reporter and RNA immunoprecipitation assays were used to evaluate the relationship among BLACAT1 and miR-149-5p and AKT1. BLACAT1 was upregulated in psoriasis tissues. Overexpression exacerbated the clinical manifestation of psoriasis and increased the epidermal thickness in imiquimod-induced mice. BLACAT1 could promote proliferation and inhibit apoptosis of keratinocytes. Further studies demonstrated that BLACAT1 positively regulated AKT1 expression, functioning as a competing endogenous RNA (ceRNA) by sponging miR-149-5p. The combination of lncRNA BLACAT1 and miR-149-5p regulates AKT1 expression and promotes psoriasis formation thus may provide a new direction for psoriasis treatment.

Retraction: Bladder cancer-associated transcript 2 contributes to nephroblastoma progression.

Retraction: Bladder cancer-associated transcript 2 contributes to nephroblastoma progression.

Yin Yang 1-stimulated long noncoding RNA bladder cancer-associated transcript 1 upregulation facilitates esophageal carcinoma progression via the microRNA-5590-3p/programmed cell death-ligand 1 pathway

ABSTRACT Esophageal carcinoma (EC) is a common gastrointestinal malignancy that poses a threat to public health worldwide. Long noncoding RNA (lncRNA) bladder cancer-associated transcript 1 (BLACAT1) exerts a tumorigenic role in several malignant tumors; nevertheless, its function in EC remains largely unknown. Besides, programmed cell death-ligand 1 (PD-L1), an oncogene in numerous human cancers, has been identified as a therapeutic target for EC. Therefore, we intended to explore the potential regulatory network involving BLACAT1 and PD-L1 in EC. In this study, we observed increased BLACAT1 and PD-L1 levels in EC tissues and EC cell lines. Moreover, YY1 could activate BLACAT1 transcription in EC cells (TE-1 and EC9706). In addition, in vitro and in vivo experiments demonstrated that BLACAT1 facilitated EC cell proliferation and metastasis and EC tumor growth. Also, the effects of BLACAT1 silencing on EC cell functions were partially reversed by PD-L1 overexpression. Besides, it was identified that BLACAT1 competed with PD-L1 to bind to miR-5590-3p in EC cells. Furthermore, miR-5590-3p suppression could abrogate the functional effects of BLACAT1 knockdown on EC cells; while PD-L1 silencing partly abolished the promoting effects of miR-5590-3p suppression on the biological functions of EC cells. To sum up, YY1-induced BLACAT1 accelerated EC progression via regulating the miR-5590-3p/PD-L1 axis.

Bladder cancer-associated transcript 2 contributes to nephroblastoma progression.

Nephroblastoma is a common pediatric kidney tumor. Existing evidence has indicated that long non-coding RNAs (lncRNAs) may be associated with tumorigenesis such as nephroblastoma. However, the contribution of lncRNA bladder cancer-associated transcript 2 (BLACAT2) to tumorigenesis and the postoperative nephroblastoma prognosis remains unknown. In total, 50 pairs of patient nephroblastoma and corresponding adjacent non-tumorous tissues were analyzed for BLACAT2 expression. The underlying roles of BLACAT2 in nephroblastoma cells were also investigated. The BLACAT2 level was detected in four nephroblastoma cell lines and normal cell line NGC-407 using a quantitative real-time polymerase chain reaction. The potential influence of BLACAT2 on nephroblastoma cells was explored based on RNA interference technology in vitro and in vivo. Moreover, the microRNA targeted by BLACAT2 and its target gene were predicted and verified. BLACAT2 silencing suppressed cell proliferation, colony formation and tumor growth in vivo and promoted cell apoptosis in vitro. Furthermore, BLACAT2 could directly bind to miR-504-3p, thereby decreasing miR-504-3p expression. In addition, the impact of miR-504-3p on proliferation, colony formation and nephroblastoma cell apoptosis was reversed by BLACAT2. Wnt11 was identified as a target of miR-504-3p. The present study revealed that a novel BLACAT2/miR-504-3p/Wnt11 axis is associated with nephroblastoma, where BLACAT2 is able to sponge miR-504-3p to down-regulate Wnt11.

Bladder cancer-associated transcript 1 promotes melanoma cell proliferation and invasion via the miR-374b-5p/U2-associated factor homology motif kinase 1 axis.

Melanoma is a malignancy derived from melanocytes and is associated with high mortality rates worldwide. Long noncoding RNAs (lncRNAs) have been confirmed to be pivotal regulators in multiple types of cancer. Many lncRNAs are aberrantly expressed in tumors and perform vital functions in cancer progression. Nevertheless, the biological role of lncRNA bladder cancer-associated transcript 1 (BLACAT1) in melanoma progression remains unexplored. In this study, the collected data showed that BLACAT1 was highly expressed in melanoma. Mechanistically, miR-374b-5p bound to BLACAT1, and U2-associated factor homology motif kinase 1 (UHMK1) was a downstream target of miR-374b-5p. BLACAT1 upregulated UHMK1 expression by acting as a competing endogenous RNA for miR-374-5b. BLACAT1 deficiency resulted in the upregulation of miR-374b-5p expression and the downregulation of UHMK1 expression in melanoma cells. Moreover, BLACAT1 activated PI3K and AKT signaling by upregulating UHMK1 expression, as shown by western blotting analyses. Functionally, UHMK1 overexpression or miR-374b-5p knockdown reversed the suppressive effect of BLACAT1 depletion on melanoma cell proliferation and invasion. In conclusion, BLACAT1 promotes melanoma cell proliferation and invasion by upregulating UHMK1 expression via miR-374b-5p to activate the PI3K/AKT pathway. These results might provide promising insight into the investigation of prognostic biomarkers of melanoma.

LncRNA BLACAT1 Accelerates Non-small Cell Lung Cancer Through Up-Regulating the Activation of Sonic Hedgehog Pathway.

Recently, increasing evidence has displayed that lncRNAs can exhibit crucial function in cancer progression, including lung cancer. LncRNA bladder cancer-associated transcript 1 (BLACAT1) is reported to participate in various cancers. The aim of our current study was to investigate the function of BLACAT1 in non-small cell lung cancer progression and study the functional pathway. Here, we reported BLACAT1 was significantly up-regulated in lung cancer tissues in comparison to the adjacent normal tissues, which suggested BLACAT1 might act as an oncogene in lung cancer. Then, A549 and PC9 cells were infected with BLACAT1 overexpression plasmid and shRNA. As shown, we proved up-regulation of BLACAT1 greatly induced the growth of non-small cell lung cancer cells. Reversely, knockdown of BLACAT1 reduced A549 and PC9 cell proliferation, migration and invasion. Sonic hedgehog (shh) signaling is able to exert a significant role in carcinogenesis, including lung cancer. Currently, we proved that up-regulation of BLACAT1 activated shh signaling pathway, via inducing shh, Gli-1 and Smo expression. shh pathway inhibitor GANT-61 reversed the effect of overexpression of BLACAT1 on non-small cell lung cancer. Moreover, we manifested that loss of BLACAT1 remarkably reduced the in vivo growth and metastasis of A549 cells via enhancing infiltrating CD3+ T cells. In conclusion, our research revealed a critical role of BLACAT1 in the modulation of non-small cell lung cancer via modulating shh pathway.

Up-regulation of long non-coding RNA BLACAT1 predicts aggressive clinicopathologic characteristics and poor prognosis of glioma.

Bladder cancer-associated transcript 1 (BLACAT1) is one of the most common cancer-associated long non-coding RNAs (lncRNAs), which has been reported as a tumor promotor in several malignancies. Previously, BLACAT1 was found to be overexpressed in glioma tissues and cell lines. Functional assays determined that BLACAT1 promoted glioma cell proliferation, migration, invasion and epithelial-mesenchymal transition, suggesting that BLACAT1 might serve as an oncogene in glioma. In the present study, we aimed to investigate its clinical significance and prognostic value in glioma patients.A total of 137 paired glioma tissue samples and adjacent normal brain tissue samples were collected from 137 glioma patients who underwent surgery from May 2014 to February 2019. The Student t test was applied to determine the statistical significance of the observed differences between 2 groups. Survival curves were constructed and differences among groups were calculated using the Kaplan–Meier method.The relative expression of BLACAT1 in glioma samples was significantly higher than that of matched normal tissues (P < .001). The expression level of tissue BLACAT1 was statistically correlated with tumor size (P = .04), Karnofsky Performance Status (KPS) (P = .006), and WHO grade (P = .017). Kaplan–Meier analysis with the log-rank test revealed that BLACAT1 up-regulation was correlated with shorter overall survival time of patients with glioma (Log Rank test, P = .012). In multivariate Cox analysis, BLACAT1 expression was found to be an independent prognostic factor for overall survival in patients with glioma (HR = 2.739; 95% CI: 1.785–8.229; P = .035). Our study demonstrates that up-regulation of BLACAT1 is able to predict aggressive clinicopathologic characteristics and poor prognosis of glioma patients. These findings may have significant implications for potential treatment options and prognosis for patients with glioma.

LncRNA BLACAT1 Promotes Proliferation, Migration and Invasion of Prostate Cancer Cells via Regulating miR-29a-3p/DVL3 Axis.

Background:Long non-coding RNA bladder cancer associated transcript 1 (BLACAT1) is oncogenic in several types of cancers. However, little is known concerning its expression and function in prostate cancer.Methods:Paired prostate cancer samples were collected, and the expression levels of BLACAT1, miR-29a-3p and disheveled segment polarity protein 3 (DVL3) were examined by quantitative real-time polymerase chain reaction (qRT-PCR); BLACAT1 shRNAs were transfected into PC-3 and LNCaP cell lines, and proliferative ability was detected by cell counting kit-8 (CCK-8) assay; qRT-PCR and Western blot were used to analyze the changes of miR-29a-3p and DVL3; dual-luciferase reporter gene assay was used to determine the regulatory relationships between miR-29a-3p and BLACAT1, and miR-29a-3p and DVL3.Results:BLACAT1 expression was significantly up-regulated in cancerous tissues of prostate cancer samples and positively correlated with the expression of DVL3, while negatively associated with miR-29a-3p. After the transfection of BLACAT1 shRNAs into prostate cancer cells, the proliferative ability and metastatic ability of cancer cells were significantly inhibited; BLACAT1 shRNAs could reduce the expression of DVL3 on both mRNA and protein expressions levels, the luciferase activity of BLACAT1 reporter was inhibited by miR-29a-3p, and DVL3 was validated as a target gene of miR-29a-3p.Conclusion:BLACAT1 expression is abnormally up-regulated in prostate cancer tissues. BLACAT1 can modulate the proliferative and metastatic ability of prostate cancer cells and have the potential to be the “ceRNA” to regulate the expression of DVL3 by sponging miR-29a-3p.

LncRNA BLACAT1/miR-519d-3p/CREB1 Axis Mediates Proliferation, Apoptosis, Migration, Invasion, and Drug-Resistance in Colorectal Cancer Progression.

BackgroundColorectal cancer (CRC) is a common severe disease around the world. The merging papers reported that long noncoding RNAs (lncRNAs) took part in the diversified pathological processes of CRC. This study aimed to uncover the role and the potential mechanism of lncRNA bladder cancer-associated transcript 1 (BLACAT1) in CRC progression.MethodsLncRNA BLACAT1, micro-519d-3p (miR-519d-3p), and cAMP-responsive element binding protein 1 (CREB1) levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in CRC tissues and cells. The bio-functional effects were examined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry assay, and transwell assay. The susceptibility testing was determined by oxaliplatin (OXA) administration. The potential binding sites between miR-519d-3p and BLACAT1 or CREB1 were predicted by online software starBase and confirmed by dual-luciferase reporter analysis. The relative proteins expression in CRC cells was determined by Western blot analysis. Xenograft tumor model was used to evaluate biological function of BLACAT1 in vivo.ResultsThe expression of BLACAT1 was promoted in CRC tissues and cells, and correlated to the TNM (tumor, node, metastasis) stage, distant metastasis, and overall survival rate. Silencing of BLACAT1 limited the proliferation, migration, and invasion, facilitated the apoptosis, and re-sensitized OXA-resistance in CRC cells. MiR-519d-3p was a target of BLACAT1. Furthermore, miR-519d-3p deletion reversed the positive effects of BLACAT1 deletion on CRC cells. Moreover, our data showed that miR-519d-3p directly targeted CREB1 and BLACAT1 sponged miR-519d-3p to regulate CREB1 expression. Besides, CREB1 disrupted the bio-functional results above from BLACAT1 suppression. Additionally, BLACAT1 knockdown promoted CRC cells sensitivity to OXA in vivo.ConclusionBLACAT1 mediated the progression of CRC and OXA-resistance by miR-519d-3p/CREB1 axis.

Effect of lncRNA-BLACAT1 on drug resistance of non-small cell lung cancer cells in DDP chemotherapy by regulating cyclin D1 expression.

The aim of this study was to investigate the effect of long non-coding ribonucleic acid (lncRNA)-bladder cancer associated transcript 1 (BLACAT1) on the drug resistance of non-small cell lung cancer (NSCLC) cells in cisplatin (DDP) chemotherapy by regulating the expression of Cyclin D1. The analysis of the lncRNA expression profiles in 483 cases of NSCLC tissues and 347 cases of cancer-adjacent tissues in Gene Expression Omnibus (GEO) database revealed that lncRNA-BLACAT1 was differentially expressed in NSCLC and related to prognosis. In order to further study its mechanism of action on DDP-resistant cells, the expression level of lncRNA-BLACAT1 in normal human lung bronchial epithelial cell line BEAS-2B, NSCLC cell line A549, and DDP-resistant cell line A549 (A549/DDP) was detected by quantitative Polymerase Chain Reaction (qPCR). LncRNA-BLACAT1 small interfering RNA (siRNA) (si-BLACAT1) and lncRNA-BLACAT1 negative control (si-NC) were transfected into A549/DPP cells. Then, qPCR was carried out to detect the changes in the expression of lncRNA-BLACAT1 before and after transfection. Thereafter, cell cycle and cell growth rate were detected by flow cytometry and the cell growth curve. Besides, the changes in cell migration, cell apoptosis, and Cyclin D1 were detected via wound healing assay, flow cytometry, and Western blotting (WB). In GEO database, lncRNA-BLACAT1 was significantly overexpressed in NSCLC (p<0.05), and the prognosis of NSCLC in BLACAT1 low-expression group was better than that in the BLACAT1 high-expression group (p<0.0001). Compared with that in BEAS-2B cells, BLACAT messenger RNA (mRNA) was notably highly expressed in A549 cells (p<0.05), and compared with that in A549 cells, BLACAT1 mRNA in A549/DPP was significantly highly expressed in A549/DDP cells (p<0.05). Additionally, in comparison with that in the si-NC group, the content of lncRNA-BLACAT1 in si-BLACAT1 group was remarkably decreased (p<0.01). Moreover, flow cytometry detection of cell cycle revealed that compared with those in si-NC group, G0/G1 phase was markedly prolonged and S phase was shortened in si-BLACAT1 group. MTS assay manifested that the absorbance at 450 nm in si-BLACAT1 group was evidently decreased on the 3rd day compared with that in the si-NC group (p<0.05), and the difference between the two groups was the most significant on the 5th day (p<0.001). According to wound healing assay, compared with those in si-NC group, the distance between cells became larger, the cell migration ability was remarkably weakened (p<0.05), and cell apoptosis was prominently reduced in si-BLACAT1 group (p<0.05). WB results showed that compared with si-NC group, si-BLACAT1 group had significantly reduced Cyclin D1 (p<0.05) CONCLUSIONS: LncRNA-BLACAT1 regulates the expression of Cyclin D1, reduces the malignant phenotype of drug-resistant cells, and increases the sensitivity of lung cancer cells to DDP.

Long Non-Coding RNA BLACAT1 in Human Cancers.

Long non-coding RNAs (lncRNAs) are a cluster of RNAs with more than 200 nucleotides in length, which lack protein-coding capacity. They are important regulators of numerous cellular processes, including gene transcription, translation, and posttranslational modification, especially in tumor initiation and progression. Aberrant expression of lncRNA bladder cancer–associated transcript 1 (BLACAT1) has been reported in various human cancers and was usually associated with unfavorable prognosis. Previous studies have revealed that dysregulation of BLACAT1 could promote the proliferation and metastasis of cancer cells. In this review, we summarize the present understanding of the functions and underlying mechanisms of BLACAT1 in the occurrence and development of various human cancers and discuss the roles of this lncRNA in cancers, including its promising application as a prognostic biomarker or a novel therapeutic target for malignancies.

The functions and mechanisms of BLACAT1 in malignant tumors

Long non-coding RNAs (lncRNAs) are a kind of transcripts which are longer than 200nt and have not protein-coding ability due to the lack of an open reading frame. However, lncRNAs can be involved in tumorigenesis and progression in various ways at the transcriptional and post-transcriptional levels. Bladder cancer associated transcript 1 (BLACAT1) as a lncRNA located on human chromosome 1q32.1, is ectopic expression in various tumors (bladder cancer, gastric malignant tumor, lung carcinoma, et al) and can regulate tumor cell proliferation, anti-apoptosis, invasion and metastasis by different mechanisms leading to occurrence and development of tumors. In this review, we summarized current studies of the functions and mechanisms of BLACAT1 in malignant tumors. Key words: RNA, long noncoding; Bladder cancer associated transcript 1; Neoplasms; Therapeutic target; Review

Expression levels and associations of five long non-coding RNAs in gastric cancer and their clinical significance.

Gastric cancer (GC) is a type of cancer that is commonly diagnosed worldwide due to a lack of early diagnostic, prognostic and therapeutic targets for this disease. The aim of the present study was to examine the expression levels of five long non-coding RNAs, namely PTPRG antisense RNA 1 (PTPRG-AS1), forkhead box P4 antisense RNA 1 (FOXP4-AS1), bladder cancer-associated transcript 2 (BLACAT2), ZXF2 and upregulated in colorectal cancer (UCC), to study their associations with patient characteristics and assess their prognostic efficacy, in order to determine the possibility of their application as GC biomarkers. The expression levels of long non-coding RNAs (lncRNAs) were determined by reverse transcription-quantitative PCR analysis of 61 pairs of GC tissues and adjacent healthy gastric mucosa tissues and GC cell lines. The Chi-square test was conducted to assess the associations of lncRNA expression levels with clinical characteristics of patients. The effect of UCC on GC cell proliferation was determined using in vitro functional experiments. The prognostic efficacy of FOXP4-AS1, BLACAT2 and UCC were examined in the Gene Expression Profiling Interactive Analysis database and those of PTPRG-AS1 were examined in the Kaplan Meier Plot database. Gene alteration frequencies of PTPRG-AS1 and BLACAT2 in GC were identified using the cBioPortal for Cancer Genomics. PTPRG-AS1, FOXP4-AS1, BLACAT2, ZXF2 and UCC were found to be upregulated in GC cell lines and GC tissues compared with adjacent normal tissues. PTPRG-AS1 and ZXF2 expression levels were associated with the expression status of the cell proliferation marker Ki67. UCC promoted the proliferation of GC cells in vitro and was associated with lymph node metastasis. Increased expression of FOXP4-AS1 indicated a favorable outcome in terms of disease-free survival, whereas high expression of PTPRG-AS1 was associated with poor survival rates for patients in different GC risk groups. BLACAT2 gene mutation was associated with poor disease-free survival outcome for patients with GC. The results suggest that PTPRG-AS1, FOXP4-AS1, BLACAT2, ZXF2 and UCC are potential biomarkers for the detection of GC at the molecular level and may be used as potential targets for GC therapy. The individual roles of these lncRNAs may be utilized for prognostic predictions.

Prognostic and Clinicopathological Significance of Long Non-Coding RNA BLACAT1 in Cancer: An Updated Meta-Analysis and TCGA Data Review.

Although increasing evidence has shown that long non-coding RNA BLACAT1 could be aberrantly expressed and used as a prognostic marker in various cancers, the results remain inconclusive. In this study, we sought to summarize the relationship between BLACAT1 (bladder cancer associated transcript 1) and relevant clinical outcomes. Eligible studies were retrieved from the online databases PubMed and Web of Science. A meta-analysis was performed using Stata 12.0 software. The Cancer Genome Atlas (TCGA) dataset was further used to verify the results. A total of sixteen studies were included to evaluate the association of BLACAT1 with overall survival or clinicopathological features by pooled hazard ratio (HR) or odds ratio (OR) in cancer. In the pooled analyses stratified by clinicopathological features, BLACAT1 expressions were closely correlated with lymph node metastasis (OR = 2.52, 95% CI: 1.86 - 3.40, p = 0.000), histological differentiation (OR = 1.98, 95% CI 1.25 - 3.13, p = 0.004), and tumor stage (OR = 1.89, 1.23 - 2.91, p = 0.004), but not to tumor size (OR = 1.91, 95% CI 0.96 - 3.80, p = 0.064) or distant metastasis (OR = 3.76, 95% CI: 0.90 - 15.71, p = 0.07) in cancer. Our results manifested that elevated BLACAT1 expression was markedly associated with poor overall survival (HR = 1.62, 95% CI: 1.41 - 1.84, p = 0.000) and PFS (HR = 2.10, 95% CI: 1.28 - 2.93, p < 0.001) among twelve types of solid cancers. Subgroup analysis demonstrated a significant association between high BLACAT1 expression and shorter OS in the lung cancer (HR = 2.03, 95% CI: 1.66 - 2.40, p = 0.000), colorectal cancer (HR = 1.47, 95% CI: 1.3 - 1.64, p = 0.000). Using Cox multivariate analyses, BLACAT1 expression was found to be an independent prognostic marker for OS in cancer (HR = 1.83, 95% CI: 1.37 - 2.30). TCGA dataset also confirmed that the upregulated BLACAT1 expression was significantly correlated with poor prognosis in cancer. Increased BLACAT1 expression was associated with more advanced clinicopathological features and may serve as poor prognosis in various cancers.

LncRNA BLACAT1 regulates the viability, migration and invasion of oral squamous cell carcinoma cells by targeting miR-142-5p.

Oral squamous cell carcinoma (OSCC) is one of the most common head and neck tumors with high incidence and mortality. Long noncoding RNA bladder cancer-associated transcript 1 (lncRNA BLACAT1) was involved in several cancers development. However, the roles of BLACAT1 in OSCC have not been investigated. The expressions of BLACAT1 and miR-142-5p in OSCC cells were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was evaluated by MTT assay. Cell migration and invasion were evaluated by transwell migration assay and transwell invasion assay, respectively. The protein levels of CyclinD1, p21, p27, MMP-2, MMP-9 and MMP-14 were detected by Western blot analysis. The interaction of BLACAT1 and miR-142-5p was verified by luciferase reporter assay. The expression of BLACAT1 was increased and the expression of miR-142-5p was decreased in OSCC cells. The knockdown of BLACAT1 suppressed the viability, migration and invasion of OSCC cells. miR-142-5p was identified as a target of BLACAT1 and BLACAT1 overexpression suppressed miR-142-5p expression. Furthermore, overexpression of miR-142-5p showed similar effects on OSCC cells viability, migration and invasion with BLACAT1 knockdown, and inhibition of miR-142-5p restored the effects of BLACAT1 knockdown OSCC cells viability, migration and invasion. LncRNA BLACAT1 knockdown suppressed the viability, migration and invasion of OSCC cells by sponging miR-142-5p, indicating that BLACAT1 might be a novel target for the treatment of OSCC.

Inhibition of long noncoding RNA BLACAT1 protects anesthesia-induced neural cytotoxicity in human induced pluripotent stem cells derived neurons

Strong evidence has shown that long non-coding RNAs (lncRNAs) play important roles in genetic modulations in human CNS. In this study, we utilized an in vitro model of human induced pluripotent stem cells (hiPSCs)-derived neurons, and hypothesized that lncRNA of bladder cancer associated transcript 1 (BLACAT1) had a functional role in anesthesia-induced cytotoxicity in human lineage neural cells. To test that, HiPSCs were induced toward neural cells and then treated with ketamine in vitro. We demonstrated that, ketamine induced neuronal apoptosis, neurite degeneration, and upregulated BLACAT1 gene expression. Inversely, lentiviral-induced BLACAT1 downregulation rescued ketamine-induced neural cytotoxicity in hiPSCs-derived neurons. In addition, BLACAT1 downregulation was demonstrated to prevent ketamine-induced mitochondrial dysregulations by suppressing ROS and caspase 3/7 activities in hiPSCs-derived neurons. Thus, we discovered a new mechanism that inhibition of LncRNA BLACAT1 could rescue anesthesia-induced neural cytotoxicity in human induced pluripotent stem cells derived neurons.

Knockdown of lncRNA BLACAT1 reverses the resistance of afatinib to non-small cell lung cancer via modulating STAT3 signalling

Afatinib, a second-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has been approved as EGFR, HER2, HER3 and HER4 inhibitor for non-small cell lung cancer (NSCLC) treatment. However, acquired resistance to afatinib has been found in most EGFR mutant NSCLC patients. Bladder cancer associated transcript 1 (BLACAT1) is a novel long non-coding RNAs (lncRNA) that play a functional role as an oncogenic lncRNA and is associated with chemoresistance. We aimed to identify the role of BLACAT1 in afatinib-resistant NSCLC and underlying mechanisms. Afatinib-resistant NSCLC cells were established. MTT assay, colony formation assay, apoptosis analysis, qRT-PCR and western blot analysis, immunohistochemistry, and in vivo study were carried out. BLACAT1 was up-regulated in afatinib-resistant NSCLC cells. Knockdown of BLACAT1 reversed the resistance of afatinib to NSCLC cells by modulating STAT3 signalling. The results provided a potential strategy for afatinib-resistant NSCLC by targeting BLACAT1.

BLACAT1 is negatively associated with prognosis in patients with NSCLC and inhibits cell progression, metastasis and epithelial-mesenchymal transition through down-regulating Wnt/β-catenin signaling pathway.

To evaluate the clinical significance and molecular mechanism of bladder cancer-associated transcript 1 (BLACAT1) in non-small-cell lung cancer (NSCLC). Overall, 156 NSCLC cancer patients were recruited and divided into high and low BLACAT1 level group by the median value of BLACAT1 expression. The associations of BLACAT1 expression with the clinicopathological features and prognosis were evaluated. A series of in vitro assays were performed to explore the role of BLACAT1 on NSCLC progression and metastasis. Patients with high BLACAT1 expression had shorter overall survival and progression-free survival than those with low BLACAT1 expression. Multivariate analyses showed that BLACAT1 was an independent prognostic factor of survival in NSCLC patients. In vitro assays showed that the downregulation of BLACAT1 significantly suppressed cell progression, migration, and invasion. The epithelial-mesenchymal transition was also inhibited when BLACAT1 was silenced, indicated by an increase in E-cadherin expression and a decrease in vimentin expression by mediating Wnt/β-catenin signaling pathway. BLACAT1 should be a potential prognostic biomarker and therapeutic target for NSCLC.

Long non‑coding RNA bladder cancer‑associated transcript 2 contributes to disease progression, chemoresistance and poor survival of patients with colorectal cancer

Colorectal cancer (CRC) is one of the leading causes of cancer-associated mortality worldwide. Long non-coding RNAs (lncRNAs) have been revealed to modulate various biological cell processes, and are involved in the initiation and progression of different diseases, including CRC. However, the role of lncRNA bladder cancer-associated transcript 2 (BLACAT2) in CRC has not been defined. The present study aimed to investigate the role of BLACAT2 in CRC. The present study measured the expression levels of BLACAT2 in CRC cells and tissues by reverse-transcription-quantitative polymerase chain reaction, and associations among BLACAT2 expression levels, important clinicopathological parameters and patient survival were statistically evaluated. The functional role of BLACAT2 in metastasis, proliferation and drug resistance was also detected. BLACAT2 was overexpressed in CRC cells and tissues, and high BLACAT2 expression was associated with larger tumor size, and more advanced lymph node (N), metastasis (M) and tumor-NM stages. Additionally, survival analysis demonstrated that patients with high BLACAT2 expression exhibited poor overall survival. Notably, high BLACAT2 expression was identified as an independent risk factor for overall survival. Migration and invasion assays revealed that BLACAT2 promoted migration and invasion, respectively. In addition, overexpression of BLACAT2 increased colony numbers and optical density values of CRC cells in a colony formation assay and an MTT assay, respectively. Furthermore, BLACAT2 levels were significantly increased in 5-fluorouracil-resistant cells, and overexpression of BLACAT2 was markedly associated with a low cell inhibition rate. In conclusion, BLACAT2 overexpression may contribute to the metastasis, proliferation and chemoresistance of CRC cells, and high BLACAT2 expression may be a promising prognostic marker for patients with CRC.