Knockdown Of Differentiation Antagonizing Non-protein Coding RNA Research Articles

LncRNA DANCR Enhances Angiogenesis to Promote Melanoma Progression Via Sponging miR-5194.

Background and aim: As an oncogenic long noncoding RNA, differentiation antagonizing non-protein coding RNA (DANCR) was identified in many kinds of cancers. However, the specific function of DANCR in melanoma remains unclear. Here, we aimed to clarify the role of DANCR played in melanoma progression and the underlying mechanisms. Methods: TCGA data base and patients' tissue samples were used to analyzed the function of DANCR in melanoma progression. Transwell assay was used to detect cell migration and tube formation assay was employed to assess the ability of angiogenesis. Western blot, qRT-PCR, ELISA and IHC assay were used to examine VEGFB expression and secrection. Luciferase assay verified the binding of DANCR and miRNA. Results: We found that the expression of DANCR was positively related to poor clinical prognosis of melanoma. DANCR knockdown suppressed melanoma progression with a more significant suppression in vivo compared with it in vitro. Further detection showed that beyond promoting proliferation, DANCR also enhanced angiogenesis via upregulating VEGFB. Mechanistic analysis revealed that DANCR upregulating VEGFB through sponging miR-5194, which negatively regulated VEGFB expression and secretion. Conclusion: We demonstrated a novel oncogenic role DANCR played in melanoma and suggested a new avenue for melanoma therapy by targeting the DANCR/miR-5194/VEGFB signaling.

Inhibition of the lncRNA DANCR attenuates cardiomyocyte injury induced by oxygen-glucose deprivation via the miR-19a-3p/MAPK1 axis.

Long noncoding RNAs (lncRNAs) have been considered as crucial regulators of acute myocardial infarction (AMI). In this study, to analyze the effect of differentiation antagonizing nonprotein coding RNA (DANCR) of lncRNA on cardiomyocyte damage in AMI, cardiomyocyte injury was induced by oxygen-glucose deprivation (OGD). Cell counting kit-8 (CCK-8) assay and flow cytometry were used to assess cell viability and apoptosis, respectively. Quantitative real-time PCR was used to measure the expression levels of DANCR and miR-19a-3p. Bioinformatics analysis and luciferase gene reporter assay were utilized to explore the relationship among DANCR, miR-19a-3p, and mitogen-activated protein kinase 1 (MAPK1). CCK-8 and TUNEL assays were used to explore the effects of DANCR alone or plus miR-19a-3p on the viability and apoptosis of OGD/R-exposed HL-1 cells. Western blot analysis was used to detect changes in the MAPK1/ERK1/2 pathway in HL-1 cells. We found that DANCR expression and miR-19a-3p level are negatively correlated as DANCR expression is increased, while miR-19a-3p level is decreased in AMI patients' serum and OGD/R-exposed HL-1 cells. DANCR knockdown increased miR-19a-3p level, and miR-19a-3p inhibition increased DANCR expression. Moreover, DANCR directly binds to miR-19a-3p. DANCR knockdown reduced viability but induced apoptosis in OGD/R-exposed HL-1 cells, while miR-19a-3p inhibition weakens these effects. Furthermore, MAPK1 is a target of miR-19a-3p. miR-19a-3p overexpression decreases MAPK1 and ERK1/2 in HL-1 cells, while miR-19a-3p inhibition increases MAPK1 and ERK1/2 in HL-1 cells. Moreover, DANCR knockdown reduces myocardium apoptosis in mice with the left anterior descending artery ligated. DANCR knockdown effectively restores myocardial cell apoptosis by regulating the miR-19a-3p/MAPK1/ERK1/2 axis.

Krüppel-like factor 5-induced overexpression of long non-coding RNA DANCR promotes the progression of cervical cancer via repressing microRNA-145-3p to target ZEB1

ABSTRACT Long non-coding RNA (lncRNA) differentiation antagonizing non-protein coding RNA (DANCR) participates in the development of diverse cancers. Nevertheless, the impact of DANCR on cervical cancer (CC) remains largely unknown. This study aims to explore the effects of DANCR sponging microRNA-145-3p (miR-145-3p) on CC. Expression of KLF5, DANCR, miR-145-3p, and zinc finger E-box binding homeobox 1 (ZEB1) in CC and adjacent normal tissues was determined. Human CC cell lines were, respectively, treated with silenced DANCR or miR145-3p mimic/inhibitor. Then, the viability, migration, invasion, and apoptosis of CC cells were measured. The cell growth in vivo was observed as well. Chromatin immunoprecipitation assay was performed to analyze the binding of KLF5 and DANCR promoter. Interaction among DANCR, miR-145-3p, and ZEB1 was assessed. KLF5, DANCR, and ZEB1 were upregulated but miR-145-3p was downregulated in CC tissues. KLF5 activated DANCR expression and the high DANCR expression was related to tumor staging, infiltrating muscle depth and lymphatic metastasis of CC patients. Reduced DANCR or elevated miR-145-3p repressed malignant behaviors of CC cells. The tumor diameter and weight were also repressed by DANCR silencing or miR-145-3p elevation. The effect of DANCR knockdown on CC cells could be reversed by miR-145-3p inhibitor. MiR-145-3p was targeted by DANCR and ZEB1 was targeted by miR-145-3p. KLF5-induced overexpression of DANCR promotes CC progression via suppressing miR-145-3p to target ZEB1. This study may provide potential targets for CC treatment.

Long noncoding RNA differentiation antagonizing nonprotein coding RNA promotes the proliferation, invasion and migration of neuroblastoma cells via targeting β-1, 4-galactosyltransferase III by sponging miR-338-3p.

Neuroblastoma is a common malignant tumor in children, and patients often have a poor prognosis. Long noncoding RNAs (lncRNAs) are involved in the regulation of neuroblastoma progression. However, the regulatory effect of lncRNA differentiation antagonizing nonprotein coding RNA (DANCR) on neuroblastoma is still not clear. The expression levels of DANCR, miR-338-3p and β-1, 4-galactosyltransferase III (B4GALT3) were determined by quantitative real-time PCR. 3-(4, 5-dimethyl-2 thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide, flow cytometry and transwell assays were used to evaluate the proliferation, apoptosis, migration and invasion abilities of neuroblastoma cells. Moreover, western blot analysis was performed to assess the levels of B4GALT3 and the proliferation, apoptosis and migration-related proteins. Besides, a dual-luciferase reporter assay was used to verify the interactions among DANCR, miR-338-3p and B4GALT3. Mice xenograft models were used to ascertain the effect of DANCR on neuroblastoma tumor growth in vivo. Our results revealed that DANCR was highly expressed in neuroblastoma tissues and cells, and its silencing impeded the progression of neuroblastoma cells. DANCR could interact with miR-338-3p. Knockdown of miR-338-3p recovered the inhibitory effect of DANCR knockdown on neuroblastoma progression. B4GALT3 was a target of miR-338-3p. B4GALT3 overexpression reversed the suppression effect of DANCR silencing on neuroblastoma progression. In-vivo experiments further confirmed that DANCR silencing inhibited neuroblastoma tumor growth. Our results indicated that DANCR promoted B4GALT3 expression to increase the proliferation, migration and invasion of neuroblastoma cells via sponging miR-338-3p, which provided a theoretical basis for the targeted therapy of neuroblastoma.

Long non-coding DANCR targets miR-185-5p to upregulate LIM and SH3 protein 1 promoting prostate cancer via the FAK/PI3K/AKT/GSK3β/snail pathway.

Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) acts as an oncogene in different cancers, although its roles in prostate cancer are not fully reported. We aimed to explore its mechanism in facilitating the malignancy of prostate cancer. The expression of DANCR, microRNA (miR)-185-5p and LIM and SH3 protein 1 (LASP1) in 40 pairs of prostate cancer tissues and normal tissues, five prostate cancer cell lines and one epithelial cell line was assessed by a quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry, respectively. In transfected PC3 and C4-2 cells, cell proliferation, migration, invasion, cell cycle distribution and epithelial-mesenchymal transition (EMT) protein expression were tested via cell counting kit-8, wound healing, transwell, flow cytometry and western blot assays, respectively. The interactions between DANCR, miR-185-5p and LASP1 were verified by a dual-luciferase reporter assay. Rescue experiments were conducted to determine the roles of DANCR on the malignant properties of PC3 and C4-2 cells. The involvement of the signaling pathway was examined using a p-FAK inhibitor. DANCR and LASP1 expression was enhanced, whereas miR-185-5p expression was diminished in prostate cancer tissues and cell lines. Knockdown of DANCR suppressed cell proliferation, migration, invasion, G1-S transition and expression of EMT proteins of the transfected PC3 and C4-2 cells. DANCR sponged miR-185-5p to upregulate LASP1 expression. DANCR-miR-185-5p-LASP1 axis activates the FAK/PI3K/AKT/GSK3β/Snail pathway to promote the malignant properties of PC3 and C4-2 cells. These findings suggest that DANCR exerts oncogenic roles in prostate cancer via the miR-185-5p/LASP1 axis activating the FAK/PI3K/AKT/GSK3β/Snail pathway. It can be a potential biomarker in the diagnosis and monitoring of prostate cancer.

Differentiation Antagonizing Non-protein Coding RNA Knockdown Alleviates Lipopolysaccharide-Induced Inflammatory Injury and Apoptosis in Human Chondrocyte Primary Chondrocyte Cells Through Upregulating miRNA-19a-3p.

ObjectiveTo confirm the role of long noncoding RNA differentiation antagonizing non‐protein coding RNA (DANCR) in chondrocyte inflammatory injury in osteoarthritis (OA) in vitro, as well as its molecular mechanism.MethodsHuman primary chondrocytes were treated with lipopolysaccharide (LPS) to construct a chondrocyte inflammatory injury in human OA cell model. Gene expression was detected using real‐time quantitative polymerase chain reaction. Cell inflammatory injury was evaluated by Cell Counting Kit‐8 assay, flow cytometry, and enzyme‐linked immunosorbent assay. The interplay between miRNA‐19a‐3p (miR‐19a) and DANCR was validated by dual‐luciferase reporter assay and RNA immunoprecipitation.ResultsExpression of DANCR was upregulated, and miR‐19a was downregulated in human OA cartilage and LPS‐treated primary chondrocytes in vitro. Moreover, DANCR expression was inversely correlated with miR‐19a in OA patients. LPS reduced cell viability and increased the apoptotic rate and secretion of interleukin (IL)‐1β, IL‐6, IL‐8, as well as tumor necrosis factor (TNF)‐α in primary chondrocyte cells in vitro, suggesting an inflammatory injury model of OA. Functionally, knockdown of DANCR could attenuate LPS‐induced apoptosis and inflammatory response, as evidenced by improved cell viability, and reduced apoptotic rate and products of IL‐1β, IL‐6, IL‐8, and TNF‐α. Notably, DANCR negatively regulated miR‐19a expression, presumably via sponging. Furthermore, miR‐19a deletion eliminated the effect of DANCR knockdown on apoptosis and the inflammatory response of primary chondrocytes under LPS stress.ConclusionDifferentiation antagonizing non‐protein coding RNA silencing could protect human chondrocyte cells against LPS‐induced inflammatory injury and apoptosis through targeting miR‐19a, suggesting a vital role of the DANCR/miR‐19a axis in OA.

Long Noncoding RNA DANCR Regulates Cell Proliferation by Stabilizing SOX2 mRNA in Nasopharyngeal Carcinoma

The long noncoding RNA DANCR (differentiation antagonizing non-protein coding RNA) displays aberrant expression in various cancers. However, its clinical value and functional mechanisms in nasopharyngeal carcinoma (NPC) remain poorly understood. We found that DANCR is dramatically up-regulated in human NPC, and that it is an indicator for poor survival prognosis. DANCR knockdown suppressed cell proliferation, colony formation invitro, and tumorigenicity invivo. Mechanistic analyses demonstrated that DANCR could bind to RNA-binding protein 3 (RBM3) protein and stabilize SOX2 mRNA, resulting in NPC cell proliferation. Our findings indicate that DANCR functions as an oncogene and a potential therapeutic target for NPC.

LncRNA DANCR promotes ATG7 expression to accelerate hepatocellular carcinoma cell proliferation and autophagy by sponging miR-222-3p.

LncRNA differentiation antagonizing non-protein coding RNA (DANCR) is an oncogene in various malignant cancers, including hepatocellular carcinoma (HCC). Autophagy is an intracellular self-digestion mechanism that accelerates the progression of HCC via promoting cell survival. However, the role of lncRNA DANCR in HCC, and the mechanism of lncRNA DANCR in the regulation of autophagy in HCC remains unknown. Therefore, the aims of this study are the investigation of the role of lncRNA DANCR in HCC, and the exploration of the molecular mechanism of lncRNA DANCR in regulating autophagy of HCC cells. In this study, the expression of lncRNA DANCR, miR-222-3p, and autophagy-related gene 7 (ATG7) was detected by qRT-PCR. The cell proliferation and colony formation were measured by Cell Counting Kit-8 (CCK-8) assay and colony formation assay. And the autophagic flux was evaluated by mRFP-GFP-LC3B reporter. The autophagy related proteins were analyzed by Western blotting. Besides, the relationship between lncRNA DANCR and miR-222-3p, as well as between miR-222-3p and ATG7, was determined by Dual-Luciferase reporter system. We found high expression of lncRNA DANCR and ATG7, and low expression of miR-222-3p in HCC tissues and cell lines. And lncRNA DANCR positively correlated with poor survival of HCC patients. Moreover, the knockdown of lncRNA DANCR inhibited cell proliferation and autophagy of HCC cells. And we predicted and proved that lncRNA DANCR induced cell proliferation, colony formation and autophagy by increasing ATG7 and suppressing miR-222-3p. Our study demonstrates the promoting role of lncRNA DANCR in HCC, and indicates the regulatory effects of lncRNA DANCR on regulating autophagy of HCC.

LncRNA DANCR Promotes Proliferation and Metastasis of Breast Cancer Cells Through Sponging miR-4319 and Upregulating VAPB.

Background: Breast cancer is one of the most prevalent cancers that often occur in females. Long noncoding RNA differentiation antagonizing nonprotein coding RNA (DANCR) has been involved in the pathogenesis of various tumors, including breast cancer. This study aimed to investigate the role and underlying mechanism of DANCR in breast cancer. Materials and Methods: The level of DANCR was detected in breast cancer tissues and cells by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Cell apoptosis was assessed using flow cytometry. Cell migration and invasion were estimated by the Transwell assay. The relationship between DANCR, miR-4319, and vesicle-associated membrane protein-associated protein B (VAPB) was confirmed by bioinformatic analysis and dual-luciferase reporter assay. The level of microRNA-4319 (miR-4319) was tested by qRT-PCR. The expression of VAPB was measured by qRT-PCR or Western blot assay. Results: DANCR and VAPB were upregulated, while miR-4319 was downregulated in breast cancer tissues and cells. Knockdown of DANCR hindered proliferation, migration, and invasion and promoted apoptosis of breast cancer cells. DANCR knockdown inhibited breast cancer development through regulating miR-4319. Inhibition of miR-4319 restrained breast cancer cell progression by targeting VAPB. Moreover, DANCR regulated VAPB expression by sponging miR-4319 in breast cancer cells. Conclusion: DANCR facilitated breast cancer cell progression through regulating the miR-4319/VAPB axis, indicating that DANCR might be a potential biomarker and therapeutic target for breast cancer treatment.

LncRNA DANCR Promotes Sorafenib Resistance via Activation of IL-6/STAT3 Signaling in Hepatocellular Carcinoma Cells.

BackgroundHepatocellular carcinoma (HCC) is one of the major malignancies and the second most common cause of cancer-related death worldwide. Sorafenib, an approved first-line systematic treatment agent for HCC, is capable to effectively improve the survival of patients with advanced HCC. The long-noncoding RNA (lncRNA) differentiation antagonizing non-protein coding RNA (DANCR) has been reported to exert oncogenic functions in several kinds of human cancers. However, the role of lncRNA DANCR in sorafenib resistance in HCC remains unknown.MethodsThe expression levels of DANCR in HCC tissues were detected by qRT-PCR. DANCR overexpression and knockdown models were established and utilized to investigate the functional role of DANCR on sorafenib resistance in HCC cells. The MS2-binding sequences-MS2-binding protein–based RNA immunoprecipitation assay, RNA pull-down and luciferase reporter assay was used to detect the association between DANCR and PSMD10 mRNA. The activation of DANCR transcription mediated by STAT3 was assessed by luciferase reporter and chromatin immunoprecipitation assays.ResultsWe found that DANCR was significantly overexpressed in HCC tissues and associated with prognosis of HCC patients. Overexpression and knockdown experiments demonstrated that DANCR promoted sorafenib resistance in HCC cells in vitro and in vivo. Mechanistically, the role of DANCR relied largely on the association with PSMD10. DANCR stabilized PSMD10 mRNA through blocking the repressing effect of several microRNAs on PSMD10. Besides, DANCR activated IL-6/STAT3 signaling via PSMD10. Furthermore, we revealed that DANCR transcription was enhanced by the activation of IL-6/STAT3 signaling, indicating a positive feedback loop of DANCR and IL-6/STAT3 signaling.ConclusionCollectively, our study is the first to elucidate the mechanism of DANCR-mediated sorafenib resistance via PSMD10-IL-6/STAT3 signaling axis, which provides a promising target for developing new therapeutic strategy for sorafenib tolerance of HCC.

RETRACTED: LncRNA DANCR silence inhibits SOX5-medicated progression and autophagy in osteosarcoma via regulating miR-216a-5p

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Authors and Editor-in-Chief. The authors of this article have informed the editors that the human anti-LC3 antibody used in this work recognized multiple antigens in murine tissues, leading them to believe that the antibody is contaminated. This possible contamination further leads them to determine that the data generated using these antibodies, and any conclusions based on that data, cannot be considered accurate. Furthermore, the authors also report that subsequent work has revealed that the DANCR/miR-216a-5p axis plays a role in the regulation of beta-oxidation and downstream non-programmed cell death and homeostasis. They therefore have requested to retract this article as unreliable. The authors have not provided the relevant raw data for the editors' review, or the subsequent reported role of DANCR in beta-oxidation. Therefore, given the authors' loss of confidence in these findings, the Editor-in-Chief supports the decision to retract the article.

LncRNA DANCR promotes tumor growth and angiogenesis in ovarian cancer through direct targeting of miR-145.

Differentiation antagonizing non-protein coding RNA (DANCR) is a newly identified oncogenic long noncoding RNA found in various cancers. However, the functional role of DANCR in tumor angiogenesis and the underlying mechanisms are still unclear. The expression of DANCR was determined in ovarian malignant tissues and cell lines. The functional role of DANCR in tumor angiogenesis was revealed by the following methods: CD31 staining of ovarian tumor tissues, matrigel-plug assay tissues, HUVEC-related tube formation assay, and invasion assay. Enzyme-linked immunosorbent assay, Western blotting, luciferase assay, and rescue experiments were used to investigate the underlying mechanisms of DANCR-regulating angiogenesis. DANCR was upregulated in ovarian malignant tissues and ovarian cancer cells. Knockdown of DANCR efficiently impaired ovarian tumor growth through inhibition of tumor angiogenesis. Furthermore, the conditional culture medium from DANCR-knockdown ovarian cells significantly inhibited tube formation and invasion of HUVEC in vitro. Mechanistic investigation indicated that vascular endothelial growth factor A (VEGF-A, VEGF) plays a crucial role during DANCR inhibition of tumor angiogenesis in ovarian cancer. Further results demonstrated that miR-145 is the direct binding target of DANCR during regulation of VEGF expression and tumor angiogenesis in ovarian cancer cells. Collectively, DANCR plays a promotional role in tumor angiogenesis in ovarian cancer through regulation of miR-145/VEGF axis. Therefore, DANCR may be a novel therapy target for ovarian cancer.

Long Non-Coding RNA Differentiation Antagonizing Nonprotein Coding RNA (DANCR) Promotes Proliferation and Invasion of Pancreatic Cancer by Sponging miR-214-5p to Regulate E2F2 Expression

BackgroundLong non-coding RNA differentiation antagonizing nonprotein coding RNA (lncRNA DANCR) has been reported to act as an oncogene in various human cancers. The role of DANCR in development of pancreatic cancer (PC) is unknown. The aim of our research was to investigate the biological role of DANCR in PC.Material/MethodsExpressions of DANCR, miR-214-5p, and E2F2 mRNA in PC tissues and cell lines were examined by qRT-PCR. Western blotting was carried out for detection of E2F2 protein expression in PC cells. Transwell assays were used to examine the metastatic ability of PC cells, while CCK-8 and colony formation assay were applied to evaluate cell proliferation. The effects of DANCR on PC cells were assessed by knockdown in vitro and in vivo. The regulatory mechanism of competitive endogenous RNAs were obtained from bioinformatics prediction and luciferase reporter assay.ResultsDANCR was markedly upregulated in clinical tissues and cell lines of PC. High DANCR expression exhibited a significant correlation with poor prognosis. DANCR knockdown inhibited growth and metastasis of PC cells. Furthermore, DANCR acted as sponge to regulate miR-214-5p, and miR-214-5p inhibitor reversed the effects of DANCR knockdown on PC cells. Moreover, DANCR positively modulated E2F2 expression through miR-214-5p in PC cells.ConclusionsCollectively, our findings demonstrated that lncRNA DANCR/miR-214-5p/E2F2 axis acts as an oncogene in PC development, which might provide a potential target for PC therapy.

Knockdown of differentiation antagonizing non-protein coding RNA exerts anti-tumor effect by up-regulating miR-214 in endometrial carcinoma.

Differentiation antagonizing non-protein coding RNA (DANCR) is a valuable long noncoding RNA (lncRNA) that involves in the progress of various cancers. However, the functions of DANCR in endometrial carcinoma (EC) have not been validated. In the present study, we aimed to evaluate the roles of DANCR in EC and explore the underlying mechanism. Expression patterns of DANCR in EC specimens and normal control specimens were determined using qRT-PCR. DANCR was knocked down in EC cell lines (AN3CA and HEC-1B) through transfection with small interfering RNA (siRNA) targeting DANCR (si-DANCR). Cell proliferation was examined using the cell counting kit-8 (CCK-8) assay. Cell apoptosis was measured by flow cytometry. Online software starBase was used to predict the target gene of DANCR. Luciferase reporter assay was carried out to confirm the association between DANCR and the predicted target microRNA (miRNA). DANCR expression was up-regulated in EC tissues as compared to the normal control tissues. Knockdown of DANCR in AN3CA and HEC-1B cells markedly suppressed cell proliferation and induced cell apoptosis. miR-214 was found to be a target miRNA of DANCR and its expression was significantly decreased in EC tissues. Suppression of miR-214 abolished the effects of si-DANCR on cell proliferation and apoptosis in AN3CA and HEC-1B cells. DANCR played an important role in promoting tumorigenesis of EC via sponging miR-214. DANCR might serve as a therapeutic target for the treatment of EC.

Long noncoding RNA DANCR promotes nasopharyngeal carcinoma progression by interacting with STAT3, enhancing IL-6/JAK1/STAT3 signaling

Nasopharyngeal carcinoma (NPC) is the most common type of malignancy of the neck and head in Southeast Asia and North Africa. Long noncoding RNA (LncRNA) Differentiation antagonizing nonprotein coding RNA (DANCR) has been reported to exert oncogenic functions in various malignant tumors. However, whether DANCR is involved in NPC tumorgenesis and its underlying mechanisms are still unknown. In the current study, we investigated the expression and biological functions of DANCR in NPC cells and found that DANCR is highly expressed in NPC cells and IL-6 stimulation upregulates DANCR expression through an STAT3-dependent manner. Besides, DANCR knockdown attenuates IL-6-induced proliferation and invasion of NPC cells. Furthermore, DANCR specifically interacts with STAT3 to promote STAT3 activation in NPC cells. Moreover, DANCR knockdown evidently decreases IL-6 induced the association between STAT3 and JAK1 in NPC cells. In addition, we also found that DANCR also indirectly binds to JAK1 through interacting with STAT3 under IL-6 stimulation in NPC cells. Taken together, the present study for the first time demonstrates that DANCR, acting as an oncogene in NPC, promotes NPC progression by interacting with STAT3 and enhancing JAK1 binding to STAT3 to strengthen IL-6/JAK1/STAT3 signaling, suggesting that it may be a potential target to be used as a novel strategy to develop NPC therapeutics.

Long non‑coding RNA DANCR promotes nasopharyngeal carcinoma cell proliferation and migration.

Aberrant expression of numerous long non‑coding RNAs (lncRNAs) has been reported to be associated with nasopharyngeal carcinoma (NPC). The present study aimed to investigate the expression and function of lncRNA differentiation antagonizing non‑protein coding RNA (DANCR) in NPC pathogenesis. Reverse transcription‑quantitative polymerase chain reaction results suggested that DANCR was significantly upregulated in NPC cells. Overexpression of DANCR promoted 5‑8F cell proliferation and migration, as detected by Cell Counting Kit‑8, colony formation and wound healing assays. DANCR was additionally identified to inhibit apoptosis, as determined by flow cytometric analysis. Furthermore, DANCR knockdown suppressed cell proliferation and migration, and promoted cell apoptosis in SUNE‑1 cell. Western blot analysis suggested that DANCR regulated the phosphorylation of AKT serine/threonine kinase and the protein expression of PTEN in NPC cells. Knockdown of DANCR decreased tumor growth in a xenograft model following subcutaneous injection of SUNE‑1 cells. Collectively, the present results suggested that DANCR regulated the proliferation, migration and apoptosis of NPC cells.

Long non‑coding RNA DANCR promotes HMGA2‑mediated invasion in lung adenocarcinoma cells.

Long non‑coding RNAs (lncRNAs) have been reported to be key regulators in various types of cancer, including lung adenocarcinoma (LAD). The roles of the lncRNA differentiation antagonizing non‑protein coding RNA (DANCR) and high mobility group AT‑hook2 (HMGA2) in LAD remain unclear. In the present study, it was revealed that the lncRNA DANCR was upregulated in LAD tissue and cell lines, compared with para‑tumor tissue and a normal lung cell line. Additionally, elevated DANCR expression was associated with poor prognosis in the patients with LAD. Functionally, the study revealed that knockdown of DANCR inhibited invasion and HMGA2 expression in the LAD cell lines, SPCA1 and A549. Furthermore, HMGA2 was overexpressed in LAD tissue and in SPCA1 and A549 cells, compared with para‑tumor tissue and a normal lung cell line. Inhibition of HMGA2 suppressed the invasive ability of SPCA1 and A549 cells, and DANCR promoted the invasive ability via regulation of HMGA2 in SPCA1 and A549 cells. The findings of the present study revealed that DANCR promoted the invasion of LAD cells by positively regulating HMGA2. Thus, a DANCR/HMGA2 axis may be a novel potential target in the molecular treatment of LAD.

DANCR contributed to hepatocellular carcinoma malignancy via sponging miR-216a-5p and modulating KLF12.

Long noncoding RNA (lncRNA) differentiation antagonizing nonprotein coding RNA (DANCR) has been identified as an oncogene in several cancers. However, the biological function and role of DANCR in hepatocellular carcinoma (HCC) remain unclear. Our current study aimed to investigate the detailed mechanism of DANCR in HCC. We found that DANCR was significantly upregulated in HCC cell lines in comparison to LO2 cells. Then, we observed that knockdown of DANCR could greatly inhibit Huh7 and HepG2 cell proliferation. In addition, HCC cell apoptosis was increased by silence of DANCR and meanwhile, cell cycle progression was blocked in G1 phase. Apart from these, downregulation of DANCR repressed HCC cell migration and invasion ability obviously. As predicted by the bioinformatics analysis, microRNA-216a-5p (miR-216a-5p) could serve as a direct target of DANCR. MiR-216a-5p has been reported to be involved in many cancers. Here, the correlation between miR-216a-5p and DANCR was confirmed using dual-luciferase reporter assay and radioimmunoprecipitation assay. Subsequently, Kruppel-like factor 12 (KLF12) exerts an important role in different tumor types. KLF12 can function as a downstream target of miR-216a-5p. Finally, the in vivo experiments were used and the data proved that DANCR also strongly suppressed HCC tumor growth in vivo via targeting miR-216a-5p and KLF12. In conclusion, our study indicated that DANCR might provide a new perspective for HCC treatment.

LncRNA DANCR promotes cervical cancer progression by upregulating ROCK1 via sponging miR-335-5p.

Emerging evidence highlights the key regulatory roles of long noncoding RNAs (lncRNAs) in the initiation and progression of numerous malignancies. The lncRNA identified as differentiation antagonizing nonprotein coding RNA (DANCR) is a novel lncRNA widely involved in the development of multiple human cancers. However, the function of DANCR and its potential molecular mechanism in cervical cancer remain unclear. In this study, we discovered that DANCR was significantly elevated in cervical cancer tissues and cells, and was closely correlated with poor prognosis of cervical cancer patients. In addition, knockdown of DANCR inhibited proliferation, migration, and invasion of cervical cancer cells in vitro, indicating that DANCR functioned as an oncogene in cervical cancer. Moreover, we verified that DANCR could directly bind to miR-335-5p, isolating miR-335-5p from its target gene Rho-associated coiled-coil containing protein kinase 1 (ROCK1). Functional analysis showed that DANCR regulated ROCK1 expression by competitively binding to miR-335-5p. Further cellular behavioral experiments revealed that miR-335-5p mimics and ROCK1 knockdown reversed the effects of upregulated DANCR on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer cells by rescue assays. In summary, this study demonstrated that DANCR promoted cervical cancer progression by functioning as a competing endogenous RNA (ceRNA) to regulate ROCK1 expression via sponging miR-335-5p, suggesting a novel potential therapeutic target for cervical cancer.

Long noncoding RNA DANCR aggravates retinoblastoma through miR-34c and miR-613 by targeting MMP-9.

Long non-coding RNAs (lncRNAs) have been identified to play vital roles in cancers, including human retinoblastoma (RB). However, the deepgoing mechanism is still ambiguous. In present study, we investigate the biological role of lncRNA DANCR (differentiation antagonizing non-protein coding RNA) in carcinogenesis of RB. Results revealed that DANCR was up-regulated in RB tissue and cell lines. Moreover, the ectopic overexpression of DANCR indicated poor overall survivals and disease free survival (DFS) for RB patients. In vitro and in vivo experiments, DANCR knockdown suppress the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) correlated protein (N-cadherin, Vimentin) of RB cells. Bioinformatics analysis predicted that miR-34c and miR-613 targeted with 3'-UTR of DANCR, besides, miR-34c and miR-613 also targeted with 3'-UTR of MMP-9, which was validated by luciferase reporter assay. Functional experiments demonstrated that miR-34c and miR-613 could reverse the oncogenic function of DANCR in RB tumorigenesis. In conclusion, our results reveal that DANCR function as competing endogenous RNA (ceRNA) for miR-34c and miR-613 to modulate progression and metastasis in RB oncogenesis via targeting MMP-9, presenting the in-depth regulation of DANCR in RB and providing a novel insight for ceRNA mechanism for RB.