DANCR promotes HCC progression and regulates EMT by sponging miR‐27a‐3p via ROCK1/LIMK1/COFILIN1 pathway

Abstract

This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. AbstractObjectives: This research aims to verify that the long non-coding RNA differentiation antagonizing nonprotein coding RNA (LncRNA DANCR) could modulate the proliferation and metastasis of hepatocellular carcinoma (HCC), and it thus may work as a novel biomarker to render new orientation for early diagnosis and clinical therapy of HCC. Materials and methods:Firstly, qRT-PCR was used to detect the expression of genes including LncRNA DANCR and miR-27a-3p. Next, MTT assay, Ethynyldeoxyuridine (EdU) analysis and clone formation assay were used for investigating cell growth and proliferation. Meanwhile, transwell assay and wound healing assay were applied to evaluate the capacity of cell metastasis and motility, respectively. In addition, bioinformatic analysis and dual-luciferase reporter assay were applied to analyse molecular interaction. Next, we conducted immunofluorescence and Western blot for mechanic investigation. Last but not the least, xenograft tumours in nude mice were built by subcutaneously injecting Hep3B cells stably transfected with sh-NC and sh-DANCR to detect proliferation and SMMC-7721 cells stably transfected with sh-NC and sh-DANCR to investigate metastasis. Results:The results of qRT-PCR and bioinformatic analysis revealed the high expression of DANCR in HCC. DANCR accelerated proliferation and metastasis of HCC cells and the knockdown of DANCR had the opposite effect. Meanwhile, xenograft tumours in sh-DANCR group grow slower and have smaller volumes compared with negative control group. Next, the antineoplastic effect of miR-27a-3p on cell growth and motility of HCC was confirmed. In addition, we clarified that DANCR acted as a ceRNA to decoy miR-27a-3p via mediating ROCK1/LIMK1/COFILIN1 pathway. In the end, we validated that DANCR/miR-27a-3p axis regulates EMT progression by cell immunofluorescence and Western blot. Conclusions:In a word, DANCR promotes HCC development and induces EMT by decoying miR-27a-3p to regulate ROCK1/LIMK1/COFILIN1 pathway.

<p>LncRNA ASB16-AS1 Promotes Growth And Invasion Of Hepatocellular Carcinoma Through Regulating miR-1827/FZD4 Axis And Activating Wnt/β-Catenin Pathway</p>

“…Mechanistically, lncRNAs have been reported to regulate gene expression by interacting with proteins or miRNAs. 14,23 Large amounts of studies support that lncRNAs are competing endogenous RNAs (ceRNAs) for miRNAs in tumor. 9,20,21 For example, lncRNA KCNQ1OT1 promotes colon cancer chemoresistance through sponging miR-34a and upregulating ATG4B.…”

The functional roles of long noncoding RNA DANCR in Human Cancers

“…DANCR could contribute to hepatocellular carcinoma malignancy via sponging miR-216a-5p and modulating KLF12 17 . In addition, Guo et al reported that DANCR could decoy miR-27a-3p to regulate ROCK1/LIMK1/COFILIN1 pathway to promote hepatocellular carcinoma progression 18 .…”

“…Wang and Tao et al demonstrated that DANCR could directly interact with miR-216a-5p to regulate the expression of KLF12, Nanog, OCT4 and SOX2 17 , 32 . Guo et al found that DANCR could promote hepatocellular carcinoma development by decoying miR-27a-3p to regulate ROCK1/LIMK1/COFILIN pathway 18 . Wang et al revealed that DANCR could promote HSP27 expression and its mediation of proliferation/metastasis via miR-577 sponging in colorectal cancer 25 .…”

The New Biomarker for Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC) Based on Public Database Mining

“…lncRNAs act as an endogenous molecular sponge, competitively binding miRNAs via shared miRNA response elements with reverse complementary binding seed regions, and thus indirectly regulating mRNA expression levels [15]. Many scientific studies have now confirmed the ceRNA hypothesis in hepatocellular carcinoma [16], breast cancer [17], and nonsmall cell lung cancer [18]. However, analyses of the CESC ceRNA network are rare and there is a lack of verification of the corresponding clinical data.…”