The role of lncRNA MALAT1 in the regulation of hepatocyte proliferation during liver regeneration

Li, Cuicui; Chang, Lei; Chen, Zhiquan; Liu, Zhongzhong; Wang, Yanfeng; Ye, Qifa

doi:10.3892/ijmm.2017.2854

Cited by 35 publications

(23 citation statements)

References 37 publications

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“…In this respect, MALAT1 represents a remarkable functional and versatile molecule that modulates a myriad of signaling pathways, including cell cycle control,18 immune balance,23 and endothelial cell function and vessel growth 24. These phenomena, when present concurrently, escalate in complexity to entail cell proliferation and migration,25 apoptosis, fibrosis,26 and malignancy 27…”

Section: Discussionmentioning

confidence: 99%

Metastasis‐associated lung adenocarcinoma transcript 1 as a common molecular driver in the pathogenesis of nonalcoholic steatohepatitis and chronic immune‐mediated liver damage

Sookoian

Flichman

Garaycoechea

et al. 2018

Hepatology Communications

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Long noncoding RNAs (lncRNAs) are functional molecules that orchestrate gene expression. To identify lncRNAs involved in nonalcoholic fatty liver disease (NAFLD) severity, we performed a multiscale study that included: (a) systems biology modeling that indicated metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) as a candidate lncRNA for exploring disease‐related associations, (b) translational exploration in the clinical setting, and (c) mechanistic modeling. MALAT1 liver profiling was performed in three consecutive phases, including an exploratory stage (liver samples from patients with NAFLD who were morbidly obese [n = 47] and from 13 individuals with normal liver histology); a replication stage (patients with NAFLD and metabolic syndrome [n =49]); and a hypothesis‐driven stage (patients with chronic hepatitis C and autoimmune liver diseases, [n = 65]). Liver abundance of MALAT1 was associated with NAFLD severity (P = 1 × 10–6); MALAT1 expression levels were up‐regulated 1.75‐fold (P = 0.029) and 3.6‐fold (P = 0.012) in patients with nonalcoholic steatohepatitis compared to those diagnosed with simple steatosis (discovery and replication set, respectively; analysis of covariance adjusted by age, homeostasis model assessment, and body mass index). Quantification of liver vascular endothelial growth factor A messenger RNA, a target of MALAT1, revealed a significant correlation between the two RNAs (R, 0.58; P = 5 × 10–8). Increased levels of MALAT1 were also associated with autoimmune liver diseases. Interactome assessment uncovered significant biological pathways, including Janus kinase‐signal transducers and activators of transcription and response to interferon‐γ. Conclusion: Deregulated expression of MALAT1 stratifies patients into the histologic phenotypes associated with NAFLD severity. MALAT1 up‐regulation seems to be a common molecular mechanism in immune‐mediated chronic inflammatory liver damage. This suggests that convergent pathophenotypes (inflammation and fibrosis) share similar molecular mediators. (Hepatology Communications 2018;2:654‐665)

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Section: Discussionmentioning

confidence: 99%

Metastasis‐associated lung adenocarcinoma transcript 1 as a common molecular driver in the pathogenesis of nonalcoholic steatohepatitis and chronic immune‐mediated liver damage

Sookoian

Flichman

Garaycoechea

et al. 2018

Hepatology Communications

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“…Sp3 and Sp1 were found to upregulate MALAT1 while MIT (Sp1 binding inhibitor) was found to downregulate it which reveals an avenue of targeting MALAT1 using MIT . It should be noted that p53 may function as a negative regulator of MALAT1, which promotes proliferation during liver regeneration via the Wnt/ β ‐catenin pathway . The mTOR signaling pathways are considered to be a key component of the oncogenic effects of MALAT1.…”

Section: Long Noncoding Rnas Signaling In Hccmentioning

confidence: 98%

Molecular mechanisms of circular RNAs, transforming growth factor‐β, and long noncoding RNAs in hepatocellular carcinoma

Shang

Adzika

et al. 2019

Cancer Medicine

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At the heart of hepatocellular carcinoma (HCC) lies disruption of signaling pathways at the level of molecules, genes, and cells. Non‐coding RNAs (ncRNAs) have been implicated in the disease progression of HCC. For instance, dysregulated expression of circular RNAs (circRNAs) has been observed in patients with HCC. As such, these RNAs are potential therapeutic targets and diagnostic markers for HCC. Long non‐coding RNAs (lncRNAs), a type of ncRNA, have also been recognized to participate in the initiation and progression of HCC. Transforming growth factor‐beta (TGF‐β) is another element which is now recognized to play crucial roles in HCC. It has been implicated in many biological processes such as survival, immune surveillance, and cell proliferation. In HCC, TGF‐β promotes disease progression by two mechanisms: an intrinsic signaling pathway and the extrinsic pathway. Through these pathways, it modulates various microenvironment factors such as inflammatory mediators and fibroblasts. An interesting yet‐to‐be resolved concept is whether the HCC‐promoting role of TGF‐β pathways is limited to a subset of HCC patients or it is involved in the whole process of HCC development. This review summarizes recent advancements to highlight the roles of circRNAs, lncRNAs, and TGF‐β in HCC.

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“…Hypoxia can activate MALAT1 transcription by inducing the binding of HIF‐1α and HIF‐2α to HRE of the MALAT1 promoter (Luo et al, 2016; Sallé‐Lefort et al, ). The upstream of the MALAT1 start site contains five p53 binding sites, and p53 may play a major role in the regulation of liver regeneration by increasing the MALAT1 promoter activity (Jeffers et al, ; Li, Chang et al, ). However, some studies have suggested that p53 acts as a transcription repressor that binds to the Malat1 promoter.…”

Section: Molecular Mechanism Regulating Malat1 Expressionmentioning

confidence: 99%

Functions and regulatory mechanisms of metastasis‐associated lung adenocarcinoma transcript 1

Chen

Huang

et al. 2018

Journal Cellular Physiology

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Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long noncoding RNA whose transcript is around 8 kb in length. As an important stress response molecule, MALAT1 can be expressed differently under stress conditions, such as hypoxia, high glucose, hydrogen peroxide, ultraviolet irradiation, infection, and chemical stimulation. MALAT1 is involved in regulating multiple cell behaviors, such as proliferation, apoptosis, differentiation, migration, epithelial-mesenchymal transition, autophagy, and morphological maintenance. Extensive evidence show that MALAT1 plays critical roles in the physiopathological process of embryo implantation, angiogenesis, tissue inflammation, tumor progression, liver fibrosis, cardiovascular remodeling, and diabetes progression by regulating gene transcription, forming RNA-protein complexes with proteins as a structural component, regulating protein activity, assisting protein localization, mediating epigenetic changes, or by acting as a competing endogenous RNA. Furthermore, MALAT1 can affect the sensitivity of chemotherapy and radiotherapy; therefore, it could be used as a potential drug target for chemotherapy and radiotherapy sensitization. The levels of MALAT1 are reported to be overexpressed in most tumor tissues or sera, and the expression levels of MALAT1 often affect the tumor size, stage, lymph node metastasis, and distant invasion. Therefore, MALAT1 can be used as a biomarker for early diagnosis, severity assessment, or prognostic assessment. This review outlines the current understanding of the biological role and function of MALAT1. In the meantime, we have summarized the mechanisms involved in the reulation of MALAT1 expression and the mechanisms by which MALAT1 regulates the physiological and pathological processes.

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The role of lncRNA MALAT1 in the regulation of hepatocyte proliferation during liver regeneration

Cited by 35 publications

References 37 publications

Metastasis‐associated lung adenocarcinoma transcript 1 as a common molecular driver in the pathogenesis of nonalcoholic steatohepatitis and chronic immune‐mediated liver damage

Metastasis‐associated lung adenocarcinoma transcript 1 as a common molecular driver in the pathogenesis of nonalcoholic steatohepatitis and chronic immune‐mediated liver damage

Molecular mechanisms of circular RNAs, transforming growth factor‐β, and long noncoding RNAs in hepatocellular carcinoma

Functions and regulatory mechanisms of metastasis‐associated lung adenocarcinoma transcript 1

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