MALAT1: a druggable long non-coding RNA for targeted anti-cancer approaches

Amodio, Nicola; Raimondi, Lavinia; Juli, Giada; Stamato, Maria Angelica; Caracciolo, Daniele; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

doi:10.1186/s13045-018-0606-4

Cited by 281 publications

(257 citation statements)

References 195 publications

(201 reference statements)

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“…The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) [15], or Lnc-MALAT1, is an abundant and highly conserved lncRNA [16][17][18]. It was first discovered as a prognostic marker for lung cancer metastasis [19].…”

Section: Introductionmentioning

confidence: 99%

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Long Non-Coding RNA MALAT1 Protects Human Osteoblasts from Dexamethasone-Induced Injury via Activation of PPM1E-AMPK Signaling

Fan¹,

Zhang²,

Liu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Dexamethasone (Dex) induces injuries to human osteoblasts. In this study, we tested the potential role of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Lnc-MALAT1) in this process. Materials: Two established human osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts were treated with Dex. Lnc-MALAT1 expression was analyzed by quantitative real-time polymerase chain reaction assay. Cell viability, apoptosis, and death were tested by the MTT assay, histone-DNA assay, and trypan blue staining assay, respectively. AMP-activated protein kinase (AMPK) signaling was evaluated by western blotting and AMPK activity assay. Results: Lnc-MALAT1 expression was downregulated by Dex treatment in the established osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts. The level of Lnc-MALAT1 was decreased in the necrotic femoral head tissues of Dex-administered patients. In osteoblastic cells and primary human osteoblasts, forced overexpression of Lnc-MALAT1 using a lentiviral vector (LV-MALAT1) inhibited Dex-induced cell viability reduction, cell death, and apoptosis. Conversely, transfection with Lnc-MALAT1 small interfering RNA aggravated Dex-induced cytotoxicity. Transfection with LV-MALAT1 downregulated Ppm1e (protein phosphatase, Mg^2+/ Mn²⁺-dependent 1e) expression to activate AMPK signaling. Treatment of osteoblasts with AMPKα1 short hairpin RNA or dominant negative mutation (T172A) abolished LV-MALAT1-induced protection against Dex-induced cytotoxicity. Furthermore, LV-MALAT1 induced an increase in nicotinamide adenine dinucleotide phosphate activity and activation of Nrf2 signaling. Dex-induced reactive oxygen species production was significantly attenuated by LV-MALAT1 transfection in osteoblastic cells and primary osteoblasts. Conclusion: Lnc-MALAT1 protects human osteoblasts from Dex-induced injuries, possibly via activation of Ppm1e-AMPK signaling.

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Section: Introductionmentioning

confidence: 99%

“…It was first discovered as a prognostic marker for lung cancer metastasis [19]. Lnc-MALAT1 is overexpressed in various human cancers [16][17][18]. It interacts with polycomb-2 to regulate histone modifications and cell proliferation [20].…”

Section: Introductionmentioning

confidence: 99%

Long Non-Coding RNA MALAT1 Protects Human Osteoblasts from Dexamethasone-Induced Injury via Activation of PPM1E-AMPK Signaling

Fan¹,

Zhang²,

Liu³

et al. 2018

Cell Physiol Biochem

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show abstract

“…In addition, many lncRNAs are expressed in a tissue-specific and/or cell type specific manner, and are involved in various gene regulatory pathways (14, 15). Furthermore, misregulation of lncRNA expression has been linked to various diseases including neuromuscular diseases, developmental disorders, neurodegenerative diseases, and cancers (16–20). Several lncRNAs have been implicated as regulatory molecules in breast cancer progression and metastasis through different mechanisms (21, 22).…”

Section: Introductionmentioning

confidence: 99%

MaTAR25LncRNA Regulates theTensin1Gene to Impact Breast Cancer Progression

Chang

Diermeier

et al. 2020

Preprint

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SUMMARYMisregulation of long non-coding RNA genes has been linked to a wide variety of cancer types. Here we report on Mammary Tumor Associated RNA 25 (MaTAR25), a nuclear enriched and chromatin associated lncRNA that plays a role in mammary tumor cell proliferation, migration, and invasion, both in vitro and in vivo. MaTAR25 functions by interacting with purine rich element binding protein B (PURB), and associating with a major downstream target gene Tensin 1 (Tns1) to regulate its expression in trans. Knockout of MaTAR25 results in down-regulation of Tns1 leading to a reorganization of the actin cytoskeleton, and a reduction of focal adhesions and microvilli. The human ortholog of MaTAR25, LINC01271, is upregulated with human breast cancer stage and metastasis. SIGNIFICANCE LncRNAs have great potential to reveal new regulatory mechanisms of function as well as having exciting therapeutic capacity given their ease of being targeted by nucleic acid drugs. Our study of MaTAR25, and its human ortholog LINC01271, reveal an unexpected function of this lncRNA in breast cancer progression by regulating Tns1 gene expression, whose protein product is a critical component of focal adhesions linking signaling between the extracellular matrix and the actin cytoskeleton. We identified LINC01271 as the human ortholog of MaTAR25, and importantly, increased expression of LINC01271 is associated with poor patient prognosis and cancer metastasis. Our findings demonstrate that LINC01271 represents an exciting therapeutic target to alter breast cancer progression.

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“…Moreover, it has been revealed that epigenetic changes, such as miRNA deregulation, chromatin structure, and DNA methylation, are implicated in the evolution of MM . Recent findings demonstrated the crucial role of non‐coding RNAs in MM and other neoplasias …”

Section: Introductionmentioning

confidence: 99%

“…4 Recent findings demonstrated the crucial role of noncoding RNAs in MM and other neoplasias. 9,10 Due to their essential roles in the modulation of various cellular machineries involved in myelomagenesis as well as PCs development, microRNAs (miRNAs) have attracted significant attentions within MM research field. 11 MiRNAs are short non-coding RNAs that, through binding the 30-untranslated regions (30-UTRs) of target RNAs (mRNAs), regulate genes expression at the post-transcriptional level.…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs and exosomes: Small molecules with big actions in multiple myeloma pathogenesis

et al. 2019

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Multiple myeloma (MM), an incurable hematologic malignancy of plasma cells increasing in the bone marrow (BM), has a complex microenvironment made to support proliferation, survival, and drug resistance of tumor cells. MicroRNAs (miRNAs), short non‐coding RNAs regulating genes expression at posttranscriptional level, have been indicated to be functionally deregulated or abnormally expressed in MM cells. Moreover, by means of miRNAs, tumor microenvironment also modulates the function of MM cells. Consistently, it has been demonstrated that miRNA levels regulation impairs their interaction with the microenvironment of BM as well as create considerable antitumor feature even capable of overcoming the protective BM milieu. Communication between cancer stromal cells and cancer cells is a key factor in tumor progression. Finding out this interaction is important to develop effective approaches that reverse bone diseases. Exosomes, nano‐vehicles having crucial roles in cell‐to‐cell communication, through targeting their cargos (i.e., miRNAs, mRNAs, DNAs, and proteins), are implicated in MM pathogenesis.

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MALAT1: a druggable long non-coding RNA for targeted anti-cancer approaches

Cited by 281 publications

References 195 publications

Long Non-Coding RNA MALAT1 Protects Human Osteoblasts from Dexamethasone-Induced Injury via Activation of PPM1E-AMPK Signaling

Long Non-Coding RNA MALAT1 Protects Human Osteoblasts from Dexamethasone-Induced Injury via Activation of PPM1E-AMPK Signaling

MaTAR25LncRNA Regulates theTensin1Gene to Impact Breast Cancer Progression

MicroRNAs and exosomes: Small molecules with big actions in multiple myeloma pathogenesis

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