Urinary BLACAT1 as a non-invasive biomarker for bladder cancer.

BACKGROUND: Bladder cancer (BC) is recorded as the fifth most common cancer worldwide with high morbidity and mortality. The most urgent problem in BCs is the high recurrence rate as two-thirds of non-muscle-invasive bladder cancer (NMIBC) will develop into muscle-invasive bladder cancer (MIBC), which retains a feature of rapid progress and metastasis. In addition, only a limited number of biomarkers are available for diagnosing BC compared to other cancers. Hence, finding sensitive and specific biomarkers for predicting the diagnosis and prognosis of patients with BC is critically needed. Therefore, this study aimed to determine the expression and clinical significance of urinary lncRNA BLACAT1 as a non-invasively diagnostic and prognostic biomarker to detect and differentiate BCs stages. METHODS AND RESULTS: The expression levels of urinary BLACAT1 were detected by qRT-PCR assay in seventy (70) BC patients with different TNM grades (T0-T3) and twelve (12) healthy subjects as control. BLACAT1 was downregulated in superficial stages (T0 = 0.09 ± 0.02 and T1 = 0.5 ± 0.1) compared to healthy control. Furthermore, in the invasive stages, its levels started to elevate in the T2 stage (1.2 ± 0. 2), and higher levels were detected in the T3 stage with a mean value of (5.2 ± 0.6). This elevation was positively correlated with disease progression. Therefore, BLACAT1 can differentiate between metastatic and non-metastatic stages of BCs. Furthermore, its predictive values are not like to be influenced by schistosomal infection. CONCLUSIONS: Upregulation of BLACAT1 in invasive stages predicted an unfavorable prognosis for patients with BCs, as it contributes to the migration and metastasis of BCs. Therefore, we can conclude that urinary BLACAT1 may be considered a non-invasive promising metastatic biomarker for BCs.

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

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Down-regulation of lncRNA BLACAT1 inhibits ovarian cancer progression by suppressing the Wnt/ß-catenin signaling pathway via regulating miR-519d-3p.

Ovarian cancer has the highest mortality in gynecologic malignancies. LncRNA BLACAT1 serves crucial functions in various cancers, but its role in ovarian cancer has not been investigated. In this article, our team explored the role and the potential regulatory mechanism of BLACAT1 in ovarian cancer. Quantitative RT-PCR showed that BLACAT1 was aberrantly up-regulated in ovarian cancer tissues compared with normal tissues. In vitro, BLACAT1 knockdown induced cell cycle arrest and inhibited the proliferation, migration and invasion of ovarian cancer cells using flow cytometry, MTT and EdU assays, wound healing assay and transwell assay, respectively. Luciferase assay verified the binding relationship between microRNA-519d-3p and lncRNA BLACAT1, and BLACAT1 negatively regulated the expression of miR-519d-3p. We also found that miR-519d-3p overexpression could inhibit ovarian cancer cells proliferation, migration and invasion. Further, Western blot demonstrated that the expression of RPS15A and nuclear ß-catenin expression was markedly reduced by BLACAT1 knockdown, and cytoplasmic ß-catenin level was not obviously affected. In vivo, BLACAT1 knockdown inhibited the tumor growth, and immunohistochemistry showed that ki67 expression was decreased by BLACAT1 suppression. Inhibition of BLACAT1 was sufficient to down-regulate the expression of RPS15A and nuclear ß-catenin but did not cause an obvious change in cytoplasmic ß-catenin expression. Taken together, BLACAT1 knockdown inhibited the progression of ovarian cancer by suppressing the Wnt/ß-catenin signaling pathway via regulating miR-519d-3p. Our work provided a proper understanding of the critical roles of BLACAT1 in ovarian cancer.

LncRNA BLACAT1 regulates VASP expression via binding to miR-605-3p and promotes giloma development.

Glioma, an aggressive tumor in brain, presents a very poor prognosis. Emerging evidence has demonstrated that dysfunction of long noncoding RNAs (lncRNAs) is closely related to giloma development. However, the roles of lncRNA BLACAT1 in glioma are not unknown. In this study, we utilized in vitro and in vivo experiments to explore the effects of BLACAT1 on glioma cells. BLACAT1 levels were increased in glioma tissues. Upregulation of BLACAT1 showed poor prognosis. Silencing of BLACAT1 markedly repressed glioma proliferation, migration, and invasion, and suppressed glioma growth in vivo. We also illustrated that BLACAT1 worked as the sponge for miR-605-3p and promoted VASP expression. miR-605-3p was downregulated in glioma and repressed glioma proliferation, migration, and invasion. And VASP is upregulated and contributed to glioma progression. Summarily, this study highlights the important roles of BLACAT1/miR-605-3p/VASP axis in glioma progression.

BLACAT1 predicts poor prognosis and serves as oncogenic lncRNA in small-cell lung cancer.

Bladder cancer-associated transcript 1 (BLACAT1) is a novel identified long noncoding RNA (lncRNA) in bladder cancer, and has been suggested to function as an oncogenic lncRNA in several types of human cancer. However, its involvement in the progression of small-cell lung cancer (SCLC) remained unknown. The aim of our study was to investigate the clinical value and biological function in SCLC. In our results, BLACAT1 expression was increased in SCLC tissues and cell lines compared with paired adjacent normal tissues and bronchial epithelial cell lines, respectively. In addition, BLACAT1 high-expression was obviously associated with advanced clinical stage, large tumor size, more lymph node metastasis, present distant metastasis, and poor prognosis. Furthermore, multivariate analysis indicated that high-expression of BLACAT1 acted as an independent poor prognostic factor for overall survival in SCLC cases. The loss-of-function studies suggested that of BLACAT1 suppressed SCLC cell proliferation, migration, and invasion, and induced G0/G1 phase arrest. In conclusion, BLACAT1 is associated with the malignant status and prognosis in patients with SCLC, and functions as an oncogenic lncRNA in regulating cell proliferation and motility, suggesting BLACAT1 may act as a potential target for SCLC prevention and treatment.

Evaluation on the diagnostic and prognostic values of long non-coding RNA BLACAT1 in common types of human cancer.

A growing number of evidence has indicated that long non-coding RNAs (lncRNA) may have many functions in the development and progression of cancer, and cloud serve as good diagnostic and prognostic biomarkers in cancers. However, these studies often revealed the changes of lncRNAs within a specific cancer type. Here, we focused on BLACAT1 and provided a comprehensive pan-cancer analysis to evaluate the diagnostic and prognostic values of BLACAT1. The expression data of BLACAT1 were came from the quantitative real-time polymerase chain reaction (qRT-PCR) and The Cancer Genome Atlas (TCGA) database, respectively. Our results showed that the change of serum BLACAT1 expression was similar to those in matched tissues. The expression level of BLACAT1 both in serum and tissues in multiple cancer types were significantly upregulated compared to those of matched non-cancer participants. The serum BLACAT1 had a high diagnostic performance among these 12 types of cancer. The relative AUC of serum BLACAT1 in cancer patients ranged from 0.833 to 0.967 compared to that in healthy subjects. Surprisingly, Kaplan-Meier survival analysis revealed that the high expression level of BLACAT1 was significantly associated with poor overall survival only in uterine corpus endometrial carcinoma (p = 0.002, log-rank test). These findings demonstrated that BLACAT1 could act as a non-specific diagnostic biomarker for cancers and a potential biomarker for prognosis prediction of endometrial cancer.

The prognostic significance of LncRNA BLACAT1 overexpression in various tumors: a meta-analysis.

Objective: Recent studies have revealed increasing evidence that the long non-coding RNA bladder cancer associated transcript 1 (LncRNA BLACAT1) plays an essential role in the emergence of different malignancies. This meta-analysis aimed to evaluate the prognostic significance of LncRNA BLACAT1 in various cancers. Methods: Six electronic databases (PubMed, Embase, Medline, Web of Science, China National Knowledge Infrastructure (CNKI), and the Chinese WanFang database) were comprehensively searched for relevant studies. The analysis of overall survival (OS) and clinicopathological characteristics was conducted. Results: Nineteen studies with 1,559 patients were eventually eligible to be included in this meta-analysis. High expression level of LncRNA BLACAT1 was identified to be linked with shorter OS (HR: 2.02, 95% CI: 1.66-2.46, p < 0.001) and PFS (HR: 2.424, 95% CI: 1.827-3.020, p < 0.001) in cancer patients as opposed to low expression levels. Subgroup analysis showed that analysis model (multivariate or univariate), cut-off value (mean or median), sample size (more or fewer than 100), and cancer type had little effect on OS in multiple tumors. Moreover, high LncRNA BLACAT1 expression was associated with positive lymph node metastasis (HR: 2.29, 95% CI: 1.66-3.16, p < 0.00001), advanced clinical stage (HR: 2.29, 95% CI: 1.65-3.19, p < 0.00001) and worse differentiation status (HR: 0.58, 95% CI: 0.37-0.92, p = 0.02), compared to low LncRNA BLACAT1 expression. Conclusion: The findings highlight that high LncRNA BLACAT1 expression might be detrimental and induce a worse prognosis for cancer patients.

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.

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 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.

Role of BLACAT1 in IL-1ß-Induced Human Articular Chondrocyte Apoptosis and Extracellular Matrix Degradation via the miR-149-5p/ HMGCR Axis.

BACKGROUND: Osteoarthritis (OA) is an inflammatory joint disorder with high incidence rates. Long non-coding RNAs (LncRNAs) influence OA development. OBJECTIVES: In this research, we attempt to figure out the functions of lncRNA BLACAT1 in human articular chondrocyte (HAC) apoptosis and extracellular matrix (ECM) degradation in OA. METHODS: Interleukin (IL)-1ß was employed to induce HAC damage. Cell viability and apoptosis were detected, with expression patterns of lncRNA BLACAT1, miR-149-5p, and HMGCR, and levels of Caspase-3, Caspase-9, BAX, Bcl-2, COL2A1, and SOX9 determined. Then, lncRNA BLACAT1 was silenced in IL-1ß-treated HACs to analyze its role in HAC damage. The target relations of lncRNA BLACAT1 and miR-149-5p and miR-149-5p and HMGCR were verified. In addition, combined experiments were performed as a miR-149-5p inhibitor or HMGCR overexpression was injected into cells with lncRNA BLACAT1 silencing. RESULTS: In IL-1ß-treated HACs, lncRNA BLACAT1 and HMGCR were overexpressed while miR- 149-5p was poorly expressed, along with reduced cell viability, enhanced apoptosis, elevated Caspase-3 and Caspase-9 activities, increased BAX level, decreased Bcl-2 level, and declined levels of COL2A1 and SOX9, which were reversed by lncRNA BLACAT1 silencing. LncRNA BLACAT1 targeted miR-149-5p, and miR-149-5p targeted HMGCR. miR-149-5p knockout or HMGCR overexpression annulled the inhibitory role of lncRNA BLACAT1 silencing in HAC apoptosis and ECM degradation. CONCLUSION: LncRNA BLACAT1 was overexpressed in IL-1ß-treated HACs, and the lncRNA BLACAT1/miR-149-5p/HMGCR ceRNA network promoted HAC apoptosis and ECM degradation.

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.

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.

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.

Long non-coding RNA BLACAT1, a novel promising biomarker and regulator of human cancers.

Emerging evidence has shown that aberrantly expressed long noncoding RNAs (lncRNAs) play a vital role in various biological processes of tumorigenesis. Bladder cancer associated transcript 1 (BLACAT1) is a novel lncRNA located on chromosome 1q32.1, which regulated multiple downstream targets via serving as a "sponge" for their corresponding microRNAs or by directly interacting with various regulating proteins. In this review, we summarized the role of BLACAT1 in the development and progression of different cancers. We also highlighted that BLACAT1 could be utilized as a potential biomarker and therapeutic target for human cancers.

Oncogenic roles of lncRNA BLACAT1 and its related mechanisms in human cancers.

Long non-coding RNAs (lncRNAs) play indispensable roles in mediating regulation of epigenetics, and their dysregulation is strongly associated with the initiation and progression of human cancers. Recently, lncRNA bladder cancer-associated transcript 1 (BLACAT1) has been observed to exert oncogenic effects on cancers, including glioma, breast cancer, lung cancer, hepatocellular carcinoma, gastric cancer, colorectal cancer, ovarian cancer, cervical cancer and osteosarcoma. Additional mechanical analyses have uncovered that lncRNA BLACAT1 is positively correlated with tumor stage, lymph node metastasis and distant metastasis of primary tumors via involvement with various cellular activities, thus leading to poor overall survival and progression-free survival (PFS). In this review, we generalize the oncogenic roles of BLACAT1 in multiple human cancers through correlation with clinical implications and cellular activities. Moreover, we forecast its potential clinical application as a novel biomarker and a promising therapeutic target for cancers.

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.

Long Non-coding RNA BLACAT1 Induces Tamoxifen Resistance in Human Breast Cancer by Regulating miR-503/Bcl-2 Axis.

INTRODUCTION: At present, drug resistance remains a major obstacle for breast cancer (BCa) patients who receive tamoxifen (TAM) chemotherapy. In this study, we aimed to investigate the functional role of long non-coding RNA BLACAT1 in the acquisition of TAM resistance in BCa. METHODS: TAM-resistant BCa cells were derived by exposure to 1 µM of TAM for 6 months. The expression levels of BLACAT1 and miR-503 were detected by RT-qPCR analysis. Chemosensitivity of BCa cells to TAM was measured by MTT assay. Apoptosis of BCa cells was detected by flow cytometric analysis, and the expression levels of apoptosis-related proteins were detected by Western blot analysis. The direct binding relation between BLACAT1 and miR-503 was predicted by bioinformatics analysis and verified by dual-luciferase reporter assay. RESULTS: Our findings showed that BLACAT1 was significantly upregulated in TAM-resistant BCa cells (MCF-7/TR and T47D/TR), and BLACAT1 knockdown markedly reduced the TAM resistance in these cells. Importantly, we observed that BLACAT1 might function as a competing endogenous RNA of miR-503 in MCF-7/TR and T47D/TR cells, thereby increasing the expression of oncogenic Bcl-2 protein. Rescue experiments showed that miR-503 inhibition partly blocked the inhibitory effect of BLACAT1 knockdown on TAM resistance of MCF-7/TR and T47D/TR cells. CONCLUSION: To conclude, this study revealed that overexpressed BLACAT1 induces TAM resistance in human BCa partly by regulating miR-503/Bcl-2 axis, potentially benefiting BCa treatment in the future.

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

BACKGROUND: Colorectal 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. METHODS: LncRNA 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. RESULTS: The 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. CONCLUSION: BLACAT1 mediated the progression of CRC and OXA-resistance by miR-519d-3p/CREB1 axis.

LncRNA BLACAT1 Is Upregulated in Cervical Squamous Cell Carcinoma (CSCC) and Predicts Poor Survival.

The function of oncogenic lncRNA BLACAT1 has been studied in several types of cancer, while its role in cervical squamous cell carcinoma (CSCC) is unknown. We showed that BLACAT1 was upregulated in CSCC tissue comparing to adjacent non-cancer tissue of CSCC patients. BLACAT1 expression in CSCC tissues was not affected by HPV infection. Patients with higher BLACAT1 level in CSCC tissues showed a significantly lower overall 5-year survival rate. BLACAT1 expression was inversely correlated with several tumor-suppressive miRNAs, such as miR-424 and miR-143. miR-424 and miR-143 overexpression did not significantly affect BLACAT1, while BLACAT1 overexpression caused downregulated miR-424 and miR-143. Overexpression of miR-424 and miR-143 led to inhibited migration and invasion, while BLACAT1 overexpression led to promoted migration and invasion of CSCC cells. In addition, overexpression of miR-424 and miR-143 attenuated the effects of BLACAT1 overexpression. Therefore, BLACAT1 overexpression may promote CSCC by downregulating miR-424 and miR-143.

LncRNA-BLACAT1 Facilitates Proliferation, Migration and Aerobic Glycolysis of Pancreatic Cancer Cells by Repressing CDKN1C via EZH2-Induced H3K27me3.

OBJECTIVE: To investigate the role of lncRNA-BLACAT1 in promoting H3K27 trimethylation of CDKN1C gene by recruiting EZH2 to regulate CCNE on glycolysis and mitochondrial oxidative phosphorylation of pancreatic cancer (PC) cells. METHODS: Following bioinformatic prediction, EZH2 and BLACAT1 in PC cells were interfered, and cells proliferation, migration and invasion in each group were detected. Western blotting detected the expression of key proteins of mitochondrial complex. The sub-cellular localization of BLACAT1 was tested, followed by testing the binding of CDKN1C and BLACAT1 with EZH2, followed by in vivo verification. RESULTS: Based on bioinformatic prediction, EZH2 and BLACAT1 were highly expressed in PC, while CDKN1C was lowly expressed (all P < 0.05). Interference with EZH2 and BLACAT1 inhibited cell proliferation, migration and aerobic glycolysis, and promoted mitochondrial oxidative phosphorylation (all P < 0.05). BLACAT1 promoted H3K27 trimethylation of CDKN1C through recruiting EZH2 (all P < 0.05). In vivo results showed that BLACAT1 interference inhibited tumor formation (all P < 0.05). CONCLUSION: Interference with BLACAT1 inhibits H3K27 trimethylation of CDKN1C gene by blocking EZH2 recruitment to promote CDKN1C expression and inhibit CCNE expression, thus suppressing PC cell proliferation, migration and aerobic glycolysis, and promoting mitochondrial oxidative phosphorylation.