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

Li, Dan; Tang, Xianbin; Li, Man; Zheng, Yi

doi:10.1002/jcb.28493

Cited by 47 publications

(34 citation statements)

References 36 publications

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“…By analyzing the cancer genome atlas (TCGA) database, we identified a survival-related lncRNA, DLX6-AS1, which was upregulated in GC. The lncRNA DLX6-AS1 is a 1990 bp non-coding transcript located at chromosomal band 7q21.3 that has been reported to be overexpressed in lung adenocarcinoma [12], hepatocellular cancer [13,14], renal cell cancer [15], osteosarcoma [16], glioma [17] and pancreatic cancer [18]. Nevertheless, the carcinogenesis and regulatory mechanism of DLX6-AS1 in GC remains unknown.…”

Section: Introductionmentioning

confidence: 99%

DLX6-AS1/miR-204-5p/OCT1 positive feedback loop promotes tumor progression and epithelial–mesenchymal transition in gastric cancer

Zhang

et al. 2019

Gastric Cancer

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Background Accumulating evidence indicates that long non-coding RNAs (lncRNAs) participate in progression of gastric cancer (GC). Nevertheless, the function and expression level of DLX6-AS1 in GC remain unknown. Methods We explored the sequencing data of DLX6-AS1 downloaded from The Cancer Genome Atlas. The expression of DLX6-AS1, miR-204-5p and OCT1 in 56 GC patients and GC cell lines was quantified by qRT-PCR and western blotting. Furthermore, we performed in vitro functional assays to assess proliferation, invasion and migration of GC cells by knockdown of DLX6-AS1. The expression level of epithelial-mesenchymal transition (EMT)-related genes was also determined by qRT-PCR and western blotting. Actin remodeling was detected by F-actin phalloidin staining. The luciferase reporter assay and chromatin immunoprecipitation assay was utilized to confirm the bioinformatic prediction. The function of the DLX6-AS1/miR-204-5p/OCT1 axis in GC proliferation was clarified by rescue assays. Results We first demonstrated that DLX6-AS1 was upregulated in GC tissues and cell lines and was associated with T3/T4 invasion, distant metastasis and poor clinical prognosis. Further functional analysis showed that downregulation of DLX6-AS1 inhibited GC cell proliferation, migration, invasion and EMT in vitro. Mechanistic investigation indicated that DLX6-AS1 acted as a cancer-promoting competing endogenous RNA (ceRNA) by binding miR-204-5p and upregulating OCT1. Moreover, the transcription factor OCT1 was confirmed to enhance DLX6-AS1 expression by targeting the promoter region. Conclusions This study revealed that OCT1-induced DLX6-AS1 promoted GC progression and the EMT via the miR-204-5p/OCT1 axis, suggesting that this lncRNA might be a promising prognostic biomarker and therapeutic target for GC.

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Section: Introductionmentioning

confidence: 99%

DLX6-AS1/miR-204-5p/OCT1 positive feedback loop promotes tumor progression and epithelial–mesenchymal transition in gastric cancer

Zhang

et al. 2019

Gastric Cancer

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“…Piao L et al reported that miR-424-5p expression is reduced in HCC patients and induces apoptosis of HCC cells by targeting and inhibiting YAP1 expression [28]. Li D et al observed that WEE1 is a target of miR-424-5p, and overexpression of WEE1 promotes the proliferation, migration and invasion of HCC cells [29]. Du H et al believed that miR-424-5p acting as a tumor suppressor gene can inhibit the invasive ability of HCC cells by directly regulating TRIM29, showing its potential to be a novel prognostic indicator [30].…”

Section: Discussionmentioning

confidence: 99%

MiR-424-5p regulates cell cycle and inhibits proliferation of hepatocellular carcinoma cells by targeting E2F7

et al. 2020

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Objective This study aims to explore the mechanism of the miR-424-5p/E2F7 axis in hepatocellular carcinoma (HCC) and provide new ideas for targeted therapy of HCC. Methods Bioinformatics analysis was used to identify the target differentially expressed miRNA in HCC and predict its target gene. qRT-PCR was employed to verify the expression of miR-424-5p and E2F7 mRNA in HCC cells. Western blot was performed to detect the effect of miR-424-5p ectopic expression on the protein expression of E2F7. CCK-8 was used to detect proliferative activity of HCC cells and flow cytometry was carried out for analyzing cell cycle distribution. Dual luciferase reporter assay was conducted to verify the direct targeting relationship between miR-424-5p and E2F7. Results We observed that miR-424-5p was down-regulated in HCC cells. CCK-8 showed that overexpression of miR-424-5p inhibited cell proliferation, and flow cytometry showed that miR-424-5p could block cells in G0/G1 phase. E2F7 was up-regulated in HCC cells, and E2F7 overexpression could facilitate the proliferative ability of HCC cells and promote the cell cycle progressing from G0/G1 to S phase. Furthermore, dual-luciferase reporter assay indicated that miR-424-5p could directly down-regulate E2F7 expression. Analysis on cell function demonstrated that miR-424-5p inhibited the proliferation of HCC cells and blocked cell cycle at G0/G1 phase by targeting E2F7. Conclusion Our results proved that E2F7 was a direct target of miR-424-5p, and miR-424-5p could regulate cell cycle and further inhibit the proliferation of HCC cells by targeting E2F7.

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“…Long non-coding RNA (lncRNA), defined as a group of transcripts with a length > 200 nucleotides with limited protein coding potential, have been implicated in the onset and development of different human cancers by chromatin remodeling, as well as transcriptional and post-transcriptional regulation [10,11]. For example, lncRNA DLX6-AS1 promotes liver cancer by increasing the expression of WEE1 via targeting miR-424-5p [12]; lncRNA MORT overexpression inhibits cancer cell proliferation in oral squamous cell carcinoma by downregulating ROCK1 [13]; lncRNAGIHCG induces cancer progression and chemoresistance and indicates poor prognosis in colorectal cancer [14].It has been found that lncRNA maternally expressed gene 3 (MEG3) with tumor suppressor activity was frequently either lost, mutated or decreased level in many human tumors and tumor derived cell lines [15]. For instance, lncRNA MEG3 inhibits the progression of prostate cancer by modulating miR-9-5p/QKI-5 axis [16]; Down regulation of lncRNA MEG3 promotes colorectal adenocarcinoma cell proliferation and inhibits the apoptosis by up-regulating TGF-β1 and its downstream sphingosine kinase 1 (SPHK1) [17]; lncRNA MEG3 suppresses the tumorigenesis of hemangioma by sponging miR-494 and regulating PTEN/PI3K/ AKT pathway [18].…”

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confidence: 99%

LncRNA MEG3 promotes melanoma growth, metastasis and formation through modulating miR-21/E-cadherin axis

Zhu

et al. 2020

Cancer Cell Int

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Background: Melanoma is the most aggressive type of skin cancer with high mortality rate and poor prognosis. lncRNA MEG3, a tumor suppressor, is closely related to the development of various cancers. However, the role of lncRNA MEG3 in melanoma has seldom been studied. Methods: RT-PCR was used to examine the expressions of lncRNA MEG3 and E-cadherin in melanoma patients and cell lines. Then, the biological functions of lncRNA MEG3 and E-cadherin were demonstrated by transfecting lncRNA MEG3-siRNA, lncRNA MEG3-overexpression, E-cadherin-siRNA and E-cadherin-overexpression plasmids in melanoma cell lines. Moreover, CCK8 assay and colony formation assay were utilized to assess the cell proliferation; Transwell assay was performed to evaluate the cell invasive ability; and tumor xenografts in nude mice were applied to test the tumor generation. Additionally, the target interactions among lncRNA MEG3, miR-21 and E-cadherin were determined by dual luciferase reporter assay. Finally, RT-PCR and WB were further conducted to verify the regulatory roles among lncRNA MEG3, miR-21 and E-cadherin. Results: The clinical data showed that lncRNA MEG3 and E-cadherin expressions were both declined in carcinoma tissues as compared with their para-carcinoma tissues. Moreover, lncRNA MEG3 and E-cadherin expressions in B16 cells were also higher than those in A375 and A2058 cells. Subsequently, based on the differently expressed lncRNA MEG3 and E-cadherin in these human melanoma cell lines, we chose B16, A375 and A2058 cells for the following experiments. The results demonstrated that lncRNA MEG3 could suppress the tumor growth, tumor metastasis and formation; and meanwhile E-cadherin had the same effects on tumor growth, tumor metastasis and formation. Furthermore, the analysis of Kaplan-Meier curves also confirmed that there was a positive correlation between lncRNA MEG3 and E-cadherin. Ultimately, dual luciferase assays were further used to verify that lncRNA MEG3 could directly target miR-21 which could directly target E-cadherin in turn. Additionally, the data of RT-PCR and WB revealed that knockdown of lncRNA MEG3 in B16 cells inhibited miR-21 expression and promoted E-cadherin expression, but overexpression of lncRNA MEG3 in A375 and A2058 cells presented completely opposite results. Conclusion: Our findings indicated that lncRNA MEG3 might inhibit the tumor growth, tumor metastasis and formation of melanoma by modulating miR-21/E-cadherin axis.

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

Cited by 47 publications

References 36 publications

DLX6-AS1/miR-204-5p/OCT1 positive feedback loop promotes tumor progression and epithelial–mesenchymal transition in gastric cancer

DLX6-AS1/miR-204-5p/OCT1 positive feedback loop promotes tumor progression and epithelial–mesenchymal transition in gastric cancer

MiR-424-5p regulates cell cycle and inhibits proliferation of hepatocellular carcinoma cells by targeting E2F7

LncRNA MEG3 promotes melanoma growth, metastasis and formation through modulating miR-21/E-cadherin axis

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