Long non‑coding RNA DLX6‑AS1 silencing inhibits malignant phenotypes of gastric cancer cells

Fu, Xiaodan; Tian, Yaru; Kuang, Weilu; Wen, Sailan; Guo, Wei

doi:10.3892/etm.2019.7521

Cited by 17 publications

(15 citation statements)

References 35 publications

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“…Recently illustrated lncRNAs rapidly emerged as key regulators of EMT in various types of cancers as reviewed by Heery et al 28 . And Fu et al 29 found that DLX6-AS1 promoted EMT in gastric cancer. Further analysis of biomarkers of EMT by western blot showed that Snail and N-cadherin expressions were increased, whereas γ-Catenin and E-cadherin levels were decreased in TNBC cells overexpressing DLX6-AS1.…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Zhang

et al. 2020

Cell Transplant

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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.

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Section: Discussionmentioning

confidence: 99%

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

Wang

Zhang

et al. 2020

Cell Transplant

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“…A total of 23 articles were identified for full review, 11 of which were excluded due to lack of necessary data or in vitro studies. Finally, the remaining 12 articles [8,9,11,[14][15][16][17][18][19][20][21][22] were included in this meta-analysis. These eligible studies were published between 2017 and 2019, and covered a total of 841 patients.…”

Section: Search Results and Basic Characteristics Of The Included Docmentioning

confidence: 99%

“…A study by Li et al found that DLX6-AS1 modulates gliomagenesis by competing endogenous sponging miR-197-5p to relieve E2F1 [18]. Knockdown of DLX6-AS1 suppressed the growth and invasive abilities of cancer cells by disrupting the epithelial-mesenchymal transition program in gastric cancer [11,27] and esophageal squamous cell carcinoma [28]. DLX6-AS1 was found to promote tumorigenesis through the NOTCH [15], Wnt [16], and PTEN [29] signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Qian et al indicated that DLX6-AS1 was overexpressed in gastric cancer tissues, it was positively associated with tumor size, lymph node involvement, and tumor staging [10]. Interestingly, Fu et al found that overexpression of DLX6-AS1 was related to metastasis and advanced TNM stage, but was not related to tumor size and differentiation in gastric cancer [11]. Because these studies were limited by sample size and equivocal controversial.…”

Section: Introductionmentioning

confidence: 99%

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LncRNA DLX6-AS1 as a potential molecular biomarker in the clinicopathology and prognosis of various cancers: a meta-analysis

et al. 2020

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Objective: Recent studies have shown that distal-less homeobox 6 antisense 1 （DLX6-AS1） is aberrantly expressed in various cancers and is associated with poor prognosis. This meta-analysis is designed to investigate the effects of DLX6-AS1 expression on clinicopathological features and survival outcomes. Methods: All eligible studies were searched from Pubmed, Web of Science, Embase, the Cochrane Library, and Wanfang database, up to August 2019. The literature was selected according to the inclusion and exclusion criteria listed in this work, and the quality of each eligible study was assessed. Each patient’s clinicopathological features and survival data were analyzed using Stata12.0 software. Begg’s test and sensitivity analysis were also conducted. Results: A total of 12 articles were included, covering 841 patients. Results showed that high expression of DLX6-AS1 was significantly closely associated with poor overall survival in tumor patients (HR = 2.30, 95% CI: 1.70–3.09, P < 0.01). This meta-analysis also showed that overexpression of DLX6-AS1 was significantly associated with tumor stage (P < 0.01), tumor size (P < 0.01), lymph node metastasis (P < 0.01), and distant metastasis (P < 0.01). Begg’s test suggested no publication bias. Conclusion: This meta-analysis revealed that high expression of DLX6-AS1 was related to the advanced clinicopathological characteristics of human digestive system cancers (gastric cancer, esophageal cancer, colon cancer, pancreatic cancer and hepatocellular carcinoma) and other cancers such as ovarian cancer, osteosarcoma and non-small cell lung cancer, and DLX6-AS1 has important predictive value for poor prognosis. However, more studies are needed to further corroborate these findings.

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“…The Proline insertion was localized in a Proline-rich region composed in humans by 9 residues, at N-terminus of the mature protein, not affecting Hox and Abdominal A superfamily functional domains. While DLX6 (Distal-Less Homeobox 6) gene was not involved in cancer, differently, lnc DLX6-AS1 was very recently deeply investigated, promoting tumorigenesis in pancreatic (35), colorectal (36), ovarian (37), lung (38), gastric (39) and liver (40) cancers. These contributions pointed for a role of this lncRNA in proliferation and metastasis induction and also suggested DLX6-AS1 as a potential therapeutic target (41).…”

Section: Discussionmentioning

confidence: 99%

The Search for Molecular Markers in a Gene-Orphan Case Study of a Pediatric Spinal Cord Pilocytic Astrocytoma

Martinelli

Gabriele

Manai

et al. 2020

Cancer Genomics Proteomics

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Background/Aim: We herein presented a case of pediatric spinal cord pilocytic astrocytoma diagnosed on the basis of histopathological and clinical findings. Materials and Methods: Given the paucity of data on genetic features for this tumor, we performed exome, array CGH and RNA sequencing analysis from nucleic acids isolated from a unique and not repeatable very small amount of a formalinfixed, paraffin-embedded (FFPE) specimen. Results: DNA mutation analysis, comparing tumor and normal lymphocyte peripheral DNA, evidenced few tumor-specific single nucleotide variants in DEFB119, MUC5B, NUDT1, LTBP3 and CPSF3L genes. Differently, tumor DNA was not characterized by for the main pilocytic astrocytoma gene variations, including BRAFV600E. An inframe trinucleotides insertion involving DLX6 or lnc DLX6-AS1 genes was scored in 44.9% of sequenced reads; the temporal profile of this variation on the expression of DLX-AS1 was investigated in patient`s urine-derived exosomes, reporting no significant variation in the one-year molecular follow-up. Array CGH identified a tumor microdeletion at the 6q25.3 chromosomal region, spanning 1,01 Mb and comprising ZDHHC14, SNX9, TULP4 and SYTL3 genes. The expression of these genes did not change in urine-derived exosomes during the one-year investigation period. Finally, RNAseq did not reveal any of the common pilocytic BRAF-KIAA1549 genes fusion events. Conclusion: To our knowledge, the present report is one of the first described gene-orphan case studies of a pediatric spinal cord pilocytic astrocytoma.

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Long non‑coding RNA DLX6‑AS1 silencing inhibits malignant phenotypes of gastric cancer cells

Cited by 17 publications

References 35 publications

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

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

LncRNA DLX6-AS1 as a potential molecular biomarker in the clinicopathology and prognosis of various cancers: a meta-analysis

The Search for Molecular Markers in a Gene-Orphan Case Study of a Pediatric Spinal Cord Pilocytic Astrocytoma

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