Long noncoding RNAs and tumorigenesis: genetic associations, molecular mechanisms, and therapeutic strategies

Zhang, Fan; Zhang, Liang; Zhang, Caiguo

doi:10.1007/s13277-015-4445-4

Cited by 97 publications

(75 citation statements)

References 157 publications

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“…24 Third, lncRNAs regulate protein functions by acting as scaffolds, guiding molecule (in cis or in trans), or decoys. 25,26 Of the limited number of lncRNAs examined so far, MALAT1 is well demonstrated to stimulate tumor progression. 7,27 Robust upregulation of MALAT1 is detected in a variety of cancers (including HCC) or cancers with higher metastatic potential.…”

Section: Discussionmentioning

confidence: 99%

The long non-coding RNA MALAT1 promotes the migration and invasion of hepatocellular carcinoma by sponging miR-204 and releasing SIRT1

Hou

Zhou

et al. 2017

Tumour Biol.

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Increasing evidence supports the significance of long non-coding RNA in cancer development. Several recent studies suggest the oncogenic activity of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in hepatocellular carcinoma. In this study, we explored the molecular mechanisms by which MALAT1 modulates hepatocellular carcinoma biological behaviors. We found that microRNA-204 was significantly downregulated in sh-MALAT1 HepG2 cell and 15 hepatocellular carcinoma tissues by quantitative real-time polymerase chain reaction analysis. Through bioinformatic screening, luciferase reporter assay, RNA-binding protein immunoprecipitation, and RNA pull-down assay, we identified microRNA-204 as a potential interacting partner for MALAT1. Functionally, wound-healing and transwell assays revealed that microRNA-204 significantly inhibited the migration and invasion of hepatocellular carcinoma cells. Notably, sirtuin 1 was recognized as a direct downstream target of microRNA-204 in HepG2 cells. Moreover, si-SIRT1 significantly inhibited cell invasion and migration process. These data elucidated, by sponging and competitive binding to microRNA-204, MALAT1 releases the suppression on sirtuin 1, which in turn promotes hepatocellular carcinoma migration and invasion. This study reveals a novel mechanism by which MALAT1 stimulates hepatocellular carcinoma progression and justifies targeting metastasis-associated lung adenocarcinoma transcript 1 as a potential therapy for hepatocellular carcinoma.

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Section: Discussionmentioning

confidence: 99%

The long non-coding RNA MALAT1 promotes the migration and invasion of hepatocellular carcinoma by sponging miR-204 and releasing SIRT1

Hou

Zhou

et al. 2017

Tumour Biol.

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“…Yet over 80% of our genome is actively transcribed to a set of RNA transcripts without protein-coding functions [6,7]. Long noncoding RNAs (lncRNAs) are broadly defined as RNAs over 200 nucleotides (nt) in length, which have many structural features of the mRNAs [8][9][10][11]. Accumulating evidence has demonstrated that lncRNAs play important molecular roles in regulating gene expression at the level of transcription and post-transcriptional, and chromatin modification [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Identification and Validation of Two Novel Prognostic lncRNAs in Kidney Renal Clear Cell Carcinoma

Song

Peng²,

Zhu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Kidney renal clear cell carcinoma (KIRC) is one of the most fatal malignancies due to late diagnosis and poor treatment. To improve its prognosis, a screening for molecular biomarkers of KIRC is urgently needed. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and prognosis of cancers. However, it is not clear whether lncRNAs can be used as molecular biomarkers in predicting the survival of KIRC patients. Methods: In this study, our aim was to identify lncRNAs/mRNAs signatures and their prognostic values in KIRC. The aberrant expression profile of mRNAs and lncRNAs in 529 KIRC tissues and 72 adjacent non-tumor pancreatic tissues were obtained from the Cancer Genome Atlas (TCGA). A weighted gene co-expression network analysis (WGCNA) of two key lncRNAs was constructed. We constructed an aberrant lncRNA-mRNA-miRNA ceRNA network in CESC. In addition, Gene Ontology (GO) and KEGG pathway analysis were performed. Results: Using lncRNA/mRNA expression profiling data, the overall analysis revealed that two novel lncRNA signatures (DNM1P35 and MIR155HG) and several mRNAs were found to be significantly correlated with KIRC patient’s overall analysis. Based on the target gene of the two lncRNA in co-expression network, the GO and KEGG analysis were also performed. A dysregulated lncRNA-related ceRNA network was also observed. Conclusion: These results suggested that the two novel lncRNAs signatures may act as independent prognostic biomarkers for predicting the survival of KIRC patient.

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“…With the development of functional genomics in the past several years, lncRNAs was found to be involved in the gene expression network at various levels, including chromatin modification, transcription, and posttranscriptional processing [9,11,23,24]. Recent reports have shown that aberrant expressions of lncRNAs might alter basic cellular biological processes and contribute to tumorigenesis [25].…”

Section: Discussionmentioning

confidence: 99%

HOX Antisense lincRNA HOXA-AS2 Promotes Tumorigenesis of Hepatocellular Carcinoma

Wang

Yang

Deng

et al. 2016

Cell Physiol Biochem

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Background: Recent studies reveal that long non-coding RNAs (LncRNAs) play critical roles in the proliferation and migration of human cancer. Previous report has shown that LncRNA HOXA-AS2 was involved in carcinoma processes. However, the expression and biological function of HOXA-AS2 in hepatocellular carcinoma (HCC) are poorly understood. Methods: Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of HOXA-AS2 in HCC tissues and cell lines. The relation between lncRNA HOXA-AS2 expression and clinicopathological characteristics was assessed by chi-square test. The prognosis was analyzed using Kaplan-Meier method, and compared differences between the two groups by log-rank test. The biological function of HOXA-AS2 on HCC cells were determined both in vitro and in vivo. Results: In the present study, we found that HOXA-AS2 expression was increased in HCC tissues and adjacent normal tissues and high HOXA-AS2 expression was associated with bigger tumor size, advanced tumor stage, and shorter survival time. Knockdown of HOXA-AS2 significantly inhibited HCC cell proliferation and invasion and resulted in an increase of apoptosis. Furthermore, inhibition of HOXA-AS2 in HCC cells significantly repressed tumorigenicity in nude mice. Conclusion: Our results indicated that the inhibition of HOXA-AS2 in HCC cells significantly inhibited cell proliferation in vitro and in vivo, which might provide a potential possibility for targeted therapy of HCC.

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Long noncoding RNAs and tumorigenesis: genetic associations, molecular mechanisms, and therapeutic strategies

Cited by 97 publications

References 157 publications

The long non-coding RNA MALAT1 promotes the migration and invasion of hepatocellular carcinoma by sponging miR-204 and releasing SIRT1

The long non-coding RNA MALAT1 promotes the migration and invasion of hepatocellular carcinoma by sponging miR-204 and releasing SIRT1

Identification and Validation of Two Novel Prognostic lncRNAs in Kidney Renal Clear Cell Carcinoma

HOX Antisense lincRNA HOXA-AS2 Promotes Tumorigenesis of Hepatocellular Carcinoma

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