DLX6 Antisense RNA 1 Research Articles

DLX6-AS1 regulates odonto/osteogenic differentiation in dental pulp cells under the control of BMP9 via the miR-128-3p/MAPK14 axis: A laboratory investigation.

The regenerative capacity of dental pulp relies on the odonto/osteogenic differentiation of dental pulp cells (DPCs), but dynamic microenvironmental changes hinder the process. Bone morphogenetic protein 9 (BMP9) promotes differentiation of DPCs towards an odonto/osteogenic lineage, forming dentinal-like tissue. However, the molecular mechanism underlying its action remains unclear. This study investigates the role of DLX6 antisense RNA 1 (DLX6-AS1) in odonto/osteogenic differentiation induced by BMP9. Custom RT2 profiler PCR array, quantitative Real-Time PCR (qRT-PCR) and western blots were used to investigate the expression pattern of DLX6-AS1 and its potential signal axis. Osteogenic ability was evaluated using alkaline phosphatase and alizarin red S staining. Interactions between lncRNA and miRNA, as well as miRNA and mRNA, were predicted through bioinformatic assays, which were subsequently validated via RNA immunoprecipitation and dual luciferase reporter assays. Student's t-test or one-way ANOVA with post hoc Tukey HSD tests were employed for data analysis, with a p-value of less than .05 considered statistically significant. DLX6-AS1 was upregulated upon BMP9 overexpression in DPCs, thereby promoting odonto/osteogenic differentiation. Additionally, miR-128-3p participated in BMP9-induced odonto/osteogenic differentiation by interacting with the downstream signal MAPK14. Modifying the expression of miR-128-3p and transfecting pcMAPK14/siMAPK14 had a rescue impact on odonto/osteogenic differentiation downstream of DLX6-AS1. Lastly, miR-128-3p directly interacted with both MAPK14 and DLX6-AS1. DLX6-AS1 could regulate the odonto/osteogenic differentiation of DPCs under the control of BMP9 through the miR-128-3p/MAPK14 axis.

MiR-141-3p Enhanced Radiosensitivity of CRC Cells.

Colorectal cancer (CRC) is recognized as one of the frequently diagnosed malignancies, and numerous microRNAs (miRs) are identified to be active in CRC. This work aimed to clarify the effect of miR-141-3p on the radiosensitivity of CRC cells. Firstly, CRC cell lines were cultured and applied to construct radiation-resistant CRC cells via X-ray treatment. The expression levels of miR-141-3p and long non-coding RNA DLX6 antisense RNA 1 (lncRNA DLX6-AS1) in CRC cells were measured using real-time quantitative polymerase chain reaction. After transfection with miR-141-3p mimics and 24 h treatment with 6- MV X-ray (0, 2, 4, 6 Gy), the survival fraction (SF) and the colony formation ability of CRC cells were determined using the cell counting kit-8 and colony formation methods. The interactions between miR-141-3p and DLX6-AS1 were analyzed using the dual-luciferase assay. The impact of miR-141-3p on DLX6-AS1 stability was detected after adding actinomycin-D. The role of DLX6- AS1 in the radiosensitivity of CRC cells was explored by transfecting oe-DLX6-AS1 into radiation- resistant CRC cells overexpressing miR-141-3p. The relative expression levels of miR-141-3p were downregulated in CRC cells and further declined in radiation-resistant cells. Upregulation of miR-141-3p relative expression reduced SF and the colony formation ability while amplifying the radiosensitivity of radiation-resistant CRC cells. miR-141-3p directly bound to DLX6-AS1 to reduce DLX6-AS1 stability, and therefore downregulated DLX6-AS1 expression. DLX6-AS1 overexpression counteracted the role of miR- 141-3p overexpression in amplifying the radiosensitivity of radiation-resistant CRC cells. miR-141-3p binding to DLX6-AS1 significantly decreased DLX6-AS1 stability and expression, promoting the radiosensitivity of CRC cells.

Silencing long non-coding RNA DLX6-AS1 or restoring microRNA-193b-3p enhances thyroid carcinoma cell autophagy and apoptosis via depressing HOXA1.

Long non‐coding RNA DLX6 antisense RNA 1 (DLX6‐AS1) lists a critical position in thyroid carcinoma (TC) development. However, the overall comprehension about DLX6‐AS1, microRNA (miR)‐193b‐3p and homeobox A1 (HOXA1) in TC is not thoroughly enough. Concerning to this, this work is pivoted on DLX6‐AS1/miR‐193b‐3p/HOXA1 axis in TC cell growth and autophagy. TC tissues and adjacent normal thyroid tissues were collected, in which expression of DLX6‐AS1, miR‐193b‐3p and HOXA1 was tested, together with their interactions. TC cells were transfected with DLX6‐AS1/miR‐193b‐3p‐related oligonucleotides or plasmids to test cell growth and autophagy. Tumorigenesis in nude mice was observed. DLX6‐AS1 and HOXA1 were up‐regulated, and miR‐193b‐3p was down‐regulated in TC. Depleted DLX6‐AS1 or restored miR‐193b‐3p disturbed cell growth and promoted autophagy. DLX6‐AS1 targeted miR‐193b‐3p and positively regulated HOXA1. miR‐193b‐3p inhibition mitigated the impaired tumorigenesis induced by down‐regulated DLX6‐AS1. Tumorigenesis in nude mice was consistent with that in cells. It is clear that DLX6‐AS1 depletion hinders TC cell growth and promotes autophagy via up‐regulating miR‐193b‐3p and down‐regulating HOXA1.

Silencing of long non-coding RNA DLX6-AS1 weakens neuroblastoma progression by the miR-513c-5p/PLK4 axis.

Emerging evidence has demonstrated the crucial roles of long noncoding RNAs in human cancers, including neuroblastoma (NB). DLX6 antisense RNA 1 (DLX6-AS1) has been identified as an oncogenic driver in NB. However, the mechanisms of DLX6-AS1 in NB progression are not fully understood. Our data showed that DLX6-AS1 was significantly overexpressed in NB tissues and cells. Moreover, DLX6-AS1 silencing repressed NB cell viability, colony formation, migration, and invasion, and promoted cell cycle arrest and apoptosis in vitro, as well as decreased tumor growth in vivo. Mechanistically, DLX6-AS1 operated as a miR-513c-5p sponge. MiR-513c-5p mediated the regulation of DLX6-AS1 on NB cell malignant progression in vitro. PLK4 was a target of miR-513c-5p- and DLX6-AS1-controlled PLK4 expression via sponging miR-513c-5p. Furthermore, the suppressive effect of miR-513c-5p overexpression on NB cell malignant progression in vitro was reversed by PLK4 upregulation. Our findings identified a novel regulatory mechanism, the DLX6-AS1/miR-513c-5p/PLK4 axis, in NB progression, highlighting a strong rationale for developing DLX6-AS1 as a new target for NB management.

Long non-coding RNA DLX6-AS1 mediates proliferation, invasion and apoptosis of endometrial cancer cells by recruiting p300/E2F1 in DLX6 promoter region.

Endometrial cancer features abnormal growth of cells of the inner lining of the uterus with the potential to invade to other organs. Accumulating evidence suggests that aberrant expression of long non‐coding RNA (lncRNA) may facilitate cancer progression. The aim of the present study was to identify the molecular mechanisms of the lncRNA known as DLX6 antisense RNA 1 (DLX6‐AS1) in endometrial cancer. Microarray‐based analysis was utilized to predict expression profile and possible function pattern of DLX6‐AS1 and DLX6 in endometrial cancer, and their expression was quantified in 78 clinically obtained endometrial cancer tissues and also in cell lines. We next assessed the effects of DLX6‐AS1 and DLX6 on proliferation, invasion and apoptosis of endometrial cancer cells. A mouse xenograft model was established to confirm DLX6‐AS1 functions and explore its underlying regulatory mechanisms in vivo. DLX6‐AS1 and DLX6 were highly expressed in endometrial cancer tissues and cells, and their silencing weakened the proliferative and invasive abilities of endometrial cancer cells and tumours, while promoting apoptosis. Mechanistic investigations indicated that DLX6‐AS1 formed a triplex structure with DLX6 via interaction with p300/E2F1 acetyltransferase. Thus, we find that functional up‐regulation of DLX6‐AS1 can promote endometrial cancer progression via a novel triplex mechanism that may prove to be great clinical significance for future treatments of endometrial cancer.

Knockdown of LncRNA DLX6-AS1 inhibits HK-2 cell pyroptosis via regulating miR-223-3p/NLRP3 pathway in lipopolysaccharide-induced acute kidney injury

Sepsis-induced acute kidney injury (AKI) represents a severe medical complication. Recently, there is growing evidence indicating the regulatory role of long non-coding RNAs (lncRNAs) in AKI pathophysiology. The present study investigated lncRNA DLX6 antisense RNA 1 (DLX6-AS1) expression in septic AKI patients and to decipher the relevant mechanisms underlying DLX6-AS1-mediated HK-2 cell pyroptosis in lipopolysaccharide (LPS)-induced AKI. The results revealed that DLX6-AS1 was up-regulated in the serum from septic AKI patients. DLX6-AS1 expression were positively associated with the creatinine levels in the serum from the septic AKI patients. In vitro studies showed that LPS induced cytotoxicity and enhanced DLX6-AS1 expression of HK-2 cells; increased NLR family pyrin domain containing 3 (NLRP3), interleukin (IL)-1β and IL-18 expression. DLX6-AS1 overexpression promoted cytotoxicity and pyroptosis of HK-2 cells; while DLX6-AS1 knockdown counteracted the LPS-induced cytotoxicity and pyroptosis of HK-2 cells. More importantly, DLX6-AS1 sponged miR-223-3p resulting in repression of miR-223-3p expression in HK-2 cells. MiR-223-3p could bind to the 3' untranslated region of NLRP3, which results in the suppressed NLRP3 expression of HK-2 cells. Further rescue experiments showed that enhanced miR-223-3p expression partially reversed the cytotoxicity and pyroptosis of HK-2 cells upon LPS stimulation or with DLX6-AS1 overexpression. Conclusively, this study identified enhanced DLX6-AS1 expression in the serum from AKI patients. Further mechanistic findings deciphered that DLX6-AS1 mediated LPS-mediated cytotoxicity and pyroptosis in HK-2 via miR-223-3p/NLRP3 axis.

DLX6 Antisense RNA 1 Modulates Glucose Metabolism and Cell Growth in Gastric Cancer by Targeting microRNA-4290.

Gastric cancer (GC) is one of the most commonly diagnosed malignancy worldwide. DLX6 antisense RNA 1 (DLX6-AS1) is a long noncoding RNA (lncRNA) that exhibits oncogenic effects on multiple human carcinomas. This study aimed to investigate the regulatory effect of DLX6-AS1in GCprogression. The expression of DLX6-AS1 in GC tissues and cell lines was examined. The cell viability, number of clones, and apoptosis,aerobic glycolysis, and mitochondrial respiration wasassessed. The effect of DLX6-AS1 on tumor growth in nude mice was also evaluated. DLX6-AS1 was overexpressed in GC tissues and cell lines. DLX6-AS1 knockdown by short hairpin RNA (shRNA) significantly inhibitedcell viabilityandcolony formation, and induced apoptosis. DLX6-AS1 silencing impaired aerobic glycolysis but stimulated mitochondrial respiration in GC cells. miR-4290 was confirmed as a downstream target of DLX6-AS1, and their expression levels were inversely correlated. GC cells expressing sh-DLX6-AS1 showed significantly lower level of 3-phosphoinositide-dependent protein kinase 1 (PDK1), a target of miR-4290, compared to cells expressing control shRNA. In addition, the suppressed GC cell malignancyupon DLX6-AS1 knockdown could be prominently reversed by PDK1 overexpression. Meanwhile, PDK1 overexpression enhanced aerobic glycolysis but repressed mitochondrial respiration under sh-DLX6-AS1 treatment. Furthermore, DLX6-AS1 knockdown significantly delayed the tumor growth in a mouse xenograft model inoculated with GC cells. LncRNA DLX6-AS1 regulated tumor growth and aerobic glycolysis in GC by targeting miR-4290 and PDK1, suggesting DLX6-AS1 might serve as a novel potential therapeutic target for GC treatment from bench to clinic.

The regulatory network of lncRNA DLX6-AS1/miR-149–5p/ERP44 is possibly related to the progression of preeclampsia

BackgroundLong noncoding RNA DLX6 antisense RNA 1 (DLX6-AS1) has been reported to be involved in various human diseases, however, its potential role in the pathogenesis of preeclampsia (PE) has not been fully explored. MethodsThe levels of DLX6-AS1, microRNA-149–5p (miR-149–5p) and endoplasmic reticulum protein 44 (ERP44) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Some clinicopathological parameters of PE were statistically analyzed. The cell proliferation, invasion and angiogenesis were assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT), transwell and tube formation assays, respectively. Levels of all protein were detected by western blot. The target relationship was predicted by StarBase v2.0 and confirmed by dual-luciferase reporter assay. ResultsHigher levels of DLX6-AS1 and ERP44, lower level of miR-149–5p were observed in PE placenta tissues. Compared with PE group with low DLX6-AS1 expression, the systolic blood pressure, diastolic blood pressure and proteinuria levels in the group with high DLX6-AS1 expression were higher, and the infant body weight level was lower. The role of miR-149–5p on these clinicopathological parameters of PE patients was opposite to that of DLX6-AS1, while ERP44 had the same effect as DLX6-AS1. Besides, DLX6-AS1 directly targeted miR-149–5p and miR-149–5p targeted ERP44. The inhibitory impact of DLX6-AS1 overexpression or ERP44 overexpression on proliferation and invasion of trophoblast cells as well as angiogenesis of HUVEC cells was reversed by up-regulating miR-149–5p. We also found that DLX6-AS1 could enhance ERP44 expression by sponging miR-149–5p. ConclusionDLX6-AS1 inhibited proliferation and invasion of trophoblast cells, and suppressed angiogenesis of HUVEC cells by miR-149–5p/ERP44 pathway.

LncRNA DLX6-AS1 Contributes to Epithelial–Mesenchymal Transition and Cisplatin Resistance in Triple-negative Breast Cancer via Modulating Mir-199b-5p/Paxillin Axis

Triple-negative breast cancer (TNBC) is one of the most aggressive cancer types with high recurrence, metastasis, and drug resistance. Recent studies report that long noncoding RNAs (lncRNAs)-mediated competing endogenous RNAs (ceRNA) play an important role in tumorigenesis and drug resistance of TNBC. Although elevated lncRNA DLX6 antisense RNA 1 (DLX6-AS1) has been observed to promote carcinogenesis in various cancers, the role in TNBC remained unclear. In this study, expression levels of DLX6-AS1 were increased in TNBC tissues and cell lines when compared with normal tissues or breast fibroblast cells which were determined by quantitative real-time PCR (RT-qPCR). Then, CCK-8 assay, cell colony formation assay and western blot were performed in CAL-51 cells transfected with siRNAs of DLX6-AS1 or MDA-MB-231 cells transfected with DLX6-AS1 over expression plasmids. Knock down of DLX6-AS1 inhibited cell proliferation, epithelial-mesenchymal transition (EMT), decreased expression levels of BCL2 apoptosis regulator (Bcl-2), Snail family transcriptional repressor 1 (Snail) as well as N-cadherin and decreased expression levels of cleaved caspase-3, γ-catenin as well as E-cadherin, while up regulation of DLX6-AS1 had the opposite effect. Besides, knockdown of DLX6-AS1 in CAL-51 cells or up regulation of DLX6-AS1 in MDA-MB-231 cells also decreased or increased cisplatin resistance of those cells analyzed by MTT assay. Moreover, by using dual luciferase reporter assay, RNA immunoprecipitation and RNA pull down assay, a ceRNA which was consisted by lncRNA DLX6-AS1, microRNA-199b-5p (miR-199b-5p) and paxillin (PXN) was identified. And DLX6-AS1 function through miR-199b-5p/PXN in TNBC cells. Finally, results of xenograft experiments using nude mice showed that DLX6-AS1 regulated cell proliferation, EMT and cisplatin resistance by miR-199b-5p/PXN axis in vivo. In brief, DLX6-AS1 promoted cell proliferation, EMT, and cisplatin resistance through miR-199b-5p/PXN signaling in TNBC in vitro and in vivo.

Knockdown of long noncoding RNA DLX6-AS1 inhibits migration and invasion of thyroid cancer cells by upregulating UPF1.

Recently, long non- coding RNAs (lncRNAs) have attracted much attention for their roles in tumor progression. The aim of this study was to investigate the exact role of lncRNA DLX6 antisense RNA 1 (DLX6-AS1) in the development of thyroid cancer (TC), and to explore the underlying mechanism. DLX6-AS1 expression in both TC cells and tissue samples was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Moreover, transwell assay and wound healing assay were conducted. QRT-PCR and Western blot assay were used to explore the underlying mechanism. Furthermore, the function of DLX6-AS1 was identified in vivo. DLX6-AS1 expression level in TC tissues was significantly higher than that of the corresponding normal tissues. Moreover, TC cell migration and invasion were markedly inhibited after DLX6-AS1 was knocked down in vitro. The mRNA and protein expressions of UPF1 were both remarkably up-regulated after knockdown of DLX6-AS1. Meanwhile, the expression level of UPF1 was negatively correlated with the expression of DLX6-AS1 in TC tissues. Furthermore, knockdown of DLX6-AS1 significantly inhibited tumor metastasis in vivo. Knockdown of DLX6-AS1 could inhibit TC cell migration and invasion via upregulating UPF1, which might be a potential therapeutic target in TC.

Long noncoding RNA DLX6-AS1 promotes neuroblastoma progression by regulating miR-107/BDNF pathway

BackgroundLong noncoding RNAs (lncRNAs) play essential roles in tumor progression. However, the functions and targets of lncRNAs in neuroblastoma (NB) progression still remain to be determined. In this study, we aimed to investigate the effect of lncRNA DLX6 antisense RNA 1 (DLX6-AS1) on NB and the underlying mechanism involved.MethodsThrough mining of public microarray datasets, we identify aberrantly expressed lncRNAs in NB. The gene expression levels were determined by quantitative real-time PCR, and protein expression levels were determined by western blot assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, wound-healing assay, transwell invasion assays and flow cytometry analysis were utilized to examine cell proliferation, migration, invasion and apoptosis. Luciferase reporter assay was performed to confirm the interaction between DLX6-AS1and its potential targets. Tumor xenograft assay was used to verify the role of DLX6-AS1 in NB in vivo.ResultsWe identified DLX6-AS1 was upregulated in NB by using a public microarray dataset. The expression of DLX6-AS1 was increased in NB tissues and derived cell lines, and high expression of DLX6-AS1 was positively correlated with advanced TNM stage and poor differentiation. Knockdown of DLX6-AS1 induced neuronal differentiation, apoptosis and inhibited the growth, invasion, and metastasis of NB cells in vitro and impaired tumor growth in vivo. MiR-107 was the downstream target of DLX6-AS1. MiR-107 was found to target brain‐derived neurotrophic factor (BDNF) which is an oncogene in NB. Knockdown of miR-107 or overexpression of BDNF reversed the suppression of NB progression caused by DLX6-AS1 silence.ConclusionOverall, our finding supports that DLX6-AS1 promotes NB progression by regulating miR-107/BDNF pathway, acting as a novel therapeutic target for NB.

The lncRNA DLX6-AS1 promoted cell proliferation, invasion, migration and epithelial-to-mesenchymal transition in bladder cancer via modulating Wnt/\u03b2-catenin signaling pathway

BackgroundBladder cancer is the most common human urological malignancies with poor prognosis, and the pathophysiology of bladder cancer involves multi-linkages of regulatory networks in the bladder cancer cells. Recently, the long noncoding RNAs (lncRNAs) have been extensively studied for their role on bladder cancer progression. In this study, we evaluated the expression of DLX6 Antisense RNA 1 (DLX6-AS1) in the cancerous bladder tissues and studied the possible mechanisms of DLX6-AS1 in regulating bladder cancer progression.MethodsGene expression was determined by qRT-PCR; protein expression levels were evaluated by western blot assay; in vitro functional assays were used to determine cell proliferation, invasion and migration; nude mice were used to establish the tumor xenograft model.ResultsOur results showed the up-regulation of DLX6-AS1 in cancerous bladder cancer tissues and bladder cell lines, and high expression of DLX6-AS1 was correlated with advance TNM stage, lymphatic node metastasis and distant metastasis. The in vitro experimental data showed that DLX6-AS1 overexpression promoted bladder cancer cell growth, proliferation, invasion, migration and epithelial-to-mesenchymal transition (EMT); while DLX6-AS1 inhibition exerted tumor suppressive actions on bladder cancer cells. Further results showed that DLX6-AS1 overexpression increased the activity of Wnt/β-catenin signaling, and the oncogenic role of DLX6-AS1 in bladder cancer cells was abolished by the presence of XAV939. On the other hand, DLX6-AS1 knockdown suppressed the activity of Wnt/β-catenin signaling, and the tumor-suppressive effects of DLX6-AS1 knockdown partially attenuated by lithium chloride and SB-216763 pretreatment. The in vivo tumor growth study showed that DLX6-AS1 knockdown suppressed tumor growth of T24 cells and suppressed EMT and Wnt/β-catenin signaling in the tumor tissues.ConclusionCollectively, the present study for the first time identified the up-regulation of DLX6-AS1 in clinical bladder cancer tissues and in bladder cancer cell lines. The results from in vitro and in vivo assays implied that DLX6-AS1 exerted enhanced effects on bladder cancer cell proliferation, invasion and migration partly via modulating EMT and the activity of Wnt/β-catenin signaling pathway.

The up-regulated lncRNA DLX6-AS1 in colorectal cancer promotes cell proliferation, invasion and migration via modulating PI3K/AKT/mTOR pathway.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths around the world. Recently, using the high-throughput techniques, long non-coding RNAs (lncRNAs) have been shown to play an important role in CRC progression. In the present study, we aimed to determine lncRNA DLX6 Antisense RNA 1 (DLX6-AS1) in CRC tissues and cell lines and to investigate the molecular mechanisms of DLX6-AS1 in CRC progression. Quantitative real-time PCR was performed to detect gene expression; cell counting kit-8, colony formation, cell invasion, and migration assays were performed to determine cell proliferation, invasion, and migration, respectively; caspase-3 activity assay kit was used to detect caspase-3 activity; in vivo tumor growth was evaluated in a nude mice xenograft model. DLX6-AS1 was up-regulated in 60 CRC tissues when compared to normal adjacent colorectal tissues, and high expression of DLX6-AS1 was correlated with advanced T stage and distant metastasis in CRC patients. The up-regulation of DLX6-AS1 was further confirmed in CRC cell lines. The gain-of-function assays showed that DLX6-AS1 overexpression promoted HCT116 cell proliferation, invasion, and migration, but inhibited cell apoptosis; while the loss-of-function assays showed that DLX6-AS1 knockdown exerted the opposite effects in SW480 cells. In vivo studies revealed that DLX6-AS1 knockdown suppressed tumor growth in the nude mice xenograft model. In addition, DLX6-AS1 overexpression caused an increase in the phosphorylated phosphoinositide 3-kinase (p-PI3K), p-AKT and p-mammalian target of rapamycin (mTOR) protein levels, and DLX6-AS1 knockdown had the opposite effects. Blockade of PI3K/AKT/mTOR signalling pathway by using mTOR inhibitor partially abolished the enhanced effects of DLX6-AS1 overexpression on CRC cell proliferation and metastasis. In summary, our data indicated that DLX6-AS1 promoted CRC cell proliferation, invasion, and migration but inhibited cell apoptosis via targeting PI3K/AKT/mTOR signalling pathway, suggesting the key role of DLX6-AS1 in CRC progression.

Long noncoding RNA DLX6-AS1 promotes liver cancer by increasing the expression of WEE1 via targeting miR-424-5p.

Long noncoding RNAs (lncRNAs) played an important role in tumorigenesis and development of hepatocellular carcinoma (HCC). In this study, we first demonstrated that lncRNA DLX6 antisense RNA 1 (DLX6‐AS1) was upregulated in cancer tissues and cells lines compared with normal adjacent and cell line. Knock‐down DLX6‐AS1 by transfection with small interfering RNA (siRNA) suppressed cell proliferation, migration, and invasion of HCC cells. Cell cycle analysis showed that cells transfected with siRNA were arrested in G0/G1 phase. Then, we performed dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay to show that DLX6‐AS1 could bind with miR‐424‐5p. And cotransfection inhibitor of miR‐424‐5p with siRNA of DLX6‐AS1 could abolish the inhibitory effect of siRNA of DLX6‐AS1 on cell proliferation, migration, and invasion. Moreover, we further demonstrated that the oncogene WEE1 G2 checkpoint kinase (WEE1) was the target of miR‐424‐5p and expression levels of WEE1 were positive correlation with that of DLX6‐AS1. Taken together, these results suggested that upregulated DLX6‐AS1 promoted cell proliferation, migration, and invasion of HCC through increasing expression of WEE1 via targeting miR‐424‐5p.

LncRNA DLX6-AS1 promoted cancer cell proliferation and invasion by attenuating the endogenous function of miR-181b in pancreatic cancer

BackgroundPancreatic cancer, one of the most aggressive malignancies, ranks the fourth cause of cancer-related death worldwide. Aberrantly expressed long non-coding RNAs (lncRNAs) functioned as oncogenes or tumor suppressors in pancreatic cancer. This study aimed to determine the expression of lncRNA DLX6 antisense RNA 1 (DLX6-AS1) in pancreatic cancer tissues and to explore the DLX6-AS1-related pathway in pancreatic cancer.Materials and methodsThe gene expression levels were determined by quantitative real-time PCR, and protein expression levels were determined by western blot assay. CCK-8 assay, colony formation assay and Transwell migration and invasion assays were used to examine cell proliferation, migration and invasion. Luciferase reporter assay was used to confirm the binding between DLX6-AS1and its potential targets. In vivo study used the mouse xenograft model to test the anti-tumor effect of DLX6-AS1 knockdown.ResultsThe high expression of DLX6-AS1 was observed in pancreatic cancer tissues, and high expression of DLX6-AS1 was positively correlated with larger tumor size, advanced TNM stage and lymph node metastasis. Knockdown of DLX6-AS1 dramatically impaired cancer cell proliferation, migration and invasion. MiR-181b was the downstream target of DLX6-AS1. Knockdown of miR-181b reversed the suppression of cell viability, migration and invasion abilities caused by DLX6-AS1 knockdown. MiR-181b was found to target Zinc finger E-box-binding homeobox 2 and to modulate epithelial-mesenchymal transition. Furthermore, DLX6-AS1 knockdown inhibited tumor growth and tumor metastasis in vivo.ConclusionCollectively, our data suggested that DLX6-AS1 promotes cancer cell proliferation and invasion by attenuating the endogenous function of miR-181b in pancreatic cancer.