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

Cell Proliferation, Год журнала: 2019, Номер 52(4)

Опубликована: Апрель 30, 2019

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

Язык: Английский

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Long noncoding RNA CASC11 promotes hepatocarcinogenesis and HCC progression through EIF4A3‐mediated E2F1 activation

Clinical and Translational Medicine, Год журнала: 2020, Номер 10(7)

Опубликована: Ноя. 1, 2020

Abstract Background Growing evidences have been revealing that long noncoding RNAs are vital factors in oncogenesis and tumor development. Among them, cancer susceptibility candidate 11 (CASC11) has displayed an impressively essential role various kinds of cancers including hepatocellular carcinoma (HCC). Nevertheless, its potential mechanism HCC still remain to be fully investigated. Methods CASC11 expression level was evaluated by real‐time polymerase chain reaction, western blotting, situ hybridization staining patients, prognostic effect analyzed. The tumorigenesis progression investigated cell proliferation assay, transwell extracellular acidification rate, flow cytometry, vivo xenograft model. interactions among CASC11, E2F transcription factor 1 (E2F1), eukaryotic translation initiation 4A3 (EIF4A3) were explored using quantitative reverse transcriptase RNA‐binding protein immunoprecipitation chromatin assays. Results Upregulation confirmed tissues associated with poor prognosis. Loss function assays showed inhibition suppressed cells proliferation, mobility, glucose metabolism promoted apoptosis. E2F1 significantly decreased after CASC11. Rescue experiments illustrated overexpression alleviated the suppression on vitro vivo. Mechanistically, recruited EIF4A3 enhance stability mRNA. impacted activation NF‐κB signaling PI3K/AKT/mTOR pathway further regulated PD‐L1 is important target immunotherapy. In addition, we identified YY1 could modulate binding promoter. Conclusions Our data revealed means EIF4A3‐mediated upregulation, indicating a promising diagnostic biomarker therapeutic for HCC.

Язык: Английский

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The emerging role of super enhancer-derived noncoding RNAs in human cancer

Theranostics, Год журнала: 2020, Номер 10(24), С. 11049 - 11062

Опубликована: Янв. 1, 2020

Super enhancers (SEs) are large clusters of adjacent that drive the expression genes which regulate cellular identity; SE regions can be enriched with a high density transcription factors, co-factors, and enhancer-associated epigenetic modifications. Through enhanced activation their target genes, SEs play an important role in various diseases conditions, including cancer. Recent studies have shown not only activate transcriptional coding to directly biological functions, but also non-coding RNAs (ncRNAs) indirectly functions. SE-derived ncRNAs critical roles tumorigenesis, malignant proliferation, metastasis, drug resistance, inflammatory response. Moreover, abnormal is closely related clinical pathological characterization tumors. In this review, we summarize functions tumorigenesis discuss prospective applications tumor therapy. A deeper understanding potential mechanism underlying action may provide new strategies for early diagnosis tumors targeted

Язык: Английский

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The USP21/YY1/SNHG16 axis contributes to tumor proliferation, migration, and invasion of non-small-cell lung cancer

Experimental & Molecular Medicine, Год журнала: 2020, Номер 52(1), С. 41 - 55

Опубликована: Янв. 1, 2020

Deubiquitinases (DUBs) and noncoding RNAs have been the subjects of recent extensive studies regarding their roles in lung cancer, but mechanisms involved are largely unknown. In our study, we used The Cancer Genome Atlas data set bioinformatics analyses identified USP21, a DUB, as potential contributor to oncogenesis non-small-cell cancer (NSCLC). We further demonstrated that USP21 was highly expressed NSCLCs. then conducted series vitro vivo assays explore effect on NSCLC progression underlying mechanism involved. promoted cell proliferation, migration, invasion tumor growth by stabilizing well-known oncogene, Yin Yang-1 (YY1), via mediating its deubiquitination. Furthermore, YY1 transcriptionally regulates expression SNHG16. Moreover, StarBase predicted miR-4500 targets SNHG16 USP21. A experiments indicated increased through miR-4500. summary, USP21/YY1/SNHG16 axis plays role promoting NSCLC. Therefore, USP21/YY1/SNHG16/miR-4500 may be therapeutic target treatment.

Язык: Английский

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LncRNA CRNDE facilitates epigenetic suppression of CELF2 and LATS2 to promote proliferation, migration and chemoresistance in hepatocellular carcinoma

Cell Death and Disease, Год журнала: 2020, Номер 11(8)

Опубликована: Авг. 11, 2020

Abstract Our study aimed to investigate the expression, functional significance, and related mechanism of long noncoding RNA CRNDE (colorectal neoplasia differentially expressed) in hepatocellular carcinoma (HCC) pathogenesis. The resulted revealed that was significantly overexpressed HCC tissues cell lines, statistically correlated with poor clinical outcome. knockdown markedly decreased proliferation, migration, chemoresistance. In addition, vivo experiments confirmed suppressive effect on progression. Mechanically, directly bound EZH2 (enhancer zeste homolog), SUZ12 (suppressor 12), SUV39H1, mediated their inhibition tumor suppressor genes, including CUGBP Elav-like family member 2 (CELF2) large (LATS2). CELF2 exerted involved CRNDE-mediated oncogenic effect. effects migration tumorigenesis, as well its Hippo pathway were abolished by LATS2 overexpression. Together, our work demonstrated importance progression elucidated underlying molecular mechanisms. These findings provided new insights into pathogenesis chemoresistance CRNDE.

Язык: Английский

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lncRNA TCL6 correlates with immune cell infiltration and indicates worse survival in breast cancer

Breast Cancer, Год журнала: 2020, Номер 27(4), С. 573 - 585

Опубликована: Янв. 20, 2020

Язык: Английский

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Antisense lncRNA LDLRAD4-AS1 promotes metastasis by decreasing the expression of LDLRAD4 and predicts a poor prognosis in colorectal cancer

Cell Death and Disease, Год журнала: 2020, Номер 11(2)

Опубликована: Фев. 28, 2020

Abstract Long noncoding RNAs (lncRNAs) have been revealed to play critical roles in tumor initiation and progression. The antisense lncRNA LDLRAD4-AS1 is the longest of LDLRAD4, its expression levels, cellular localization, precise function, mechanism colorectal cancer (CRC) remain unknown. In this study, we observed that was located nucleus CRC cells upregulated most specimens cell lines. Overexpression correlated with poor prognosis patients. LncRNA upregulation enhanced migration invasion vitro facilitated metastasis vivo. Mechanistic investigations suggested could decrease LDLRAD4 by disrupting stability mRNA, resulting epithelial-to-mesenchymal transition (EMT) through upregulating Snail, thereby promoting CRC. Our results demonstrated a previously unrecognized LDLRAD4-AS1-LDLRAD4-Snail regulatory axis involved epigenetic posttranscriptional regulation contributes progression metastasis.

Язык: Английский

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Long non-coding RNA NNT-AS1 affects progression of breast cancer through miR-142-3p/ZEB1 axis

Biomedicine & Pharmacotherapy, Год журнала: 2018, Номер 103, С. 939 - 946

Опубликована: Апрель 24, 2018

Язык: Английский

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Strategies to target long non-coding RNAs in cancer treatment: progress and challenges

Egyptian Journal of Medical Human Genetics, Год журнала: 2020, Номер 21(1)

Опубликована: Авг. 27, 2020

Abstract Background Long non-coding RNAs are important regulators of gene expression and diverse biological processes. Their aberrant contributes to a verity diseases including cancer development progression, providing them with great potential be diagnostic prognostic biomarkers therapeutic targets. Therefore, they can have key role in personalized medicine. This review aims at introducing possible strategies target long ncRNAs therapeutically cancer. Also, chemical modification nucleic acid-based therapeutics improve their pharmacological properties is explained. Then, approaches for the systematic delivery reagents into tumor cells or organs briefly discussed, followed by describing obstacles expansion therapeutics. Main text function as oncogenes suppressors, whose activity modulate all hallmarks They expressed very restricted spatial temporal pattern easily detected fluids patients. These make excellent targets anticancer drugs. Targeting methods aim attenuate oncogenic lncRNAs interfere lncRNA functions prevent carcinogenesis. Numerous suppression ncRNAs, alternation epigenetic effects, interfering function, restoration downregulated lost recruitment regulatory elements patterns recommended targeting shown inhibitory effects on malignancy. In this regard, proliferation, migration, invasion been inhibited apoptosis has induced different vitro vivo. Downregulation upregulation some growth factors (e.g., neurotrophic factor) achieved. Conclusions efficient safe rarely addressed. Only one clinical trial involving reported. Among technologies, RNAi most commonly used effective tool lncRNAs. However, other technologies need examined further research essential put practice.

Язык: Английский

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LINC01232 exerts oncogenic activities in pancreatic adenocarcinoma via regulation of TM9SF2

Cell Death and Disease, Год журнала: 2019, Номер 10(10)

Опубликована: Сен. 20, 2019

Abstract Pancreatic adenocarcinoma (PAAD), one of the most prevailing malignant tumors in digestive system, is identified as main culprits cancer-associated mortality. Despite long intergenic non-protein coding RNA 1232 (LINC01232) found to be upregulated TCGA PAAD tissues and associated with poor prognosis, potential LINC01232 progression still needs more explorations. In this study, was chosen research object cellular processes. Functionally, loss-of function assays were carried out experimental results indicated that suppression hindered deterioration by affecting cell proliferation migration. Furthermore, relationship between its nearby gene transmembrane 9 superfamily member 2 (TM9SF2) investigated. The same expression pattern TM9SF2 samples observed. It upregulation could a crucial factor for dysregulation TM9SF2. Mechanistically, recruited EIF4A3 boost mRNA stability. Besides, our findings demonstrated transcriptional activation mediated SP1. Therefore, we concluded executed carcinogenic properties via regulation conclusion, study first unveil role molecular mechanism LINC01232, suggesting promising target pancreatic cancer treatment.

Язык: Английский

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