Effect Of Metastasis-associated Lung Adenocarcinoma Transcript 1 Research Articles

Metastasis-associated lung adenocarcinoma transcript 1 induces methyl-CpG-binding domain protein 4 in mice with recurrent spontaneous abortion caused by anti-phospholipid antibody positivity

IntroductionAntiphospholipid syndrome is an autoimmune disease characterized by pregnancy-related morbidity, related to persistent positivity of antiphospholipid antibodies (APL). One of the characteristics of pregnancy-related morbidity in patients with antiphospholipid syndrome is recurrent spontaneous abortion (RSA). This study aimed to examine the mechanism through which metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) regulates methyl-CpG-binding domain protein 4 (MBD4) expression in APL-positive RSA. MethodsClinical samples were subjected to microarray analysis to filter differentially expressed genes. RSA mice with APL positivity were generated, followed by adenoviral vector injection to artificially upregulate MALAT1. The effects of MALAT1 on the biological behavior of trophoblast cells were assessed. The downstream mechanism of MALAT1 was analyzed using subcellular fractionation and bioinformatics prediction, and the relationship between MALAT1 and CREB binding protein (CREBBP) or MBD4 was investigated in trophoblast cells. ResultsMALAT1 was downregulated in APL-positive RSA patients. MALAT1 was predominantly localized in the nucleus and recruited CREBBP to mediate the MBD4 transcription. In the APL-positive RSA mice overexpressing MALAT1, the expression of soluble Fms-related tyrosine kinase 1 and anticardiolipin antibody and the embryonic resorption rate were decreased, indicating that MALAT1 reduced the occurrence of RSA in mice. Moreover, MALAT1 enhanced proliferation, migration, and invasion of trophoblast cells through recruiting CREBBP to promote MBD4 expression. Silencing of CREBBP or MBD4 increased embryonic resorption rate in RSA mice overexpressing MALAT1. DiscussionMALAT1 suppresses APL-positive RSA by promoting MBD4 transcription through recruitment of CREBBP to the MBD4 promoter region.

CEBPB promotes gastrointestinal motility dysfunction after severe acute pancreatitis via the MALAT1/CIRBP/ERK axis.

Severe acute pancreatitis (SAP) is a kind of reversible inflammatory process of the exocrine pancreas with gastrointestinal motility dysfunction involved. Studies have highlighted the role of long noncoding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in AP. However, the mechanism underlying its role in the gastrointestinal motility dysfunction remains undefined. Hence, we explored the regulatory role of MALAT1 in gastrointestinal motility dysfunction following SAP. Then, the expression of CCAAT/enhancer-binding protein beta (CEBPB), MALAT1 and cold-inducible RNA binding protein (CIRBP) was detected in plasma of SAP patients and pancreatic and intestinal tissues of SAP mouse models with their correlation analyzed also. Additionally, the effect of MALAT1 on the pancreatic and intestinal injury, expression of inflammatory factors and the ERK pathway-related genes as well as gastrointestinal motility dysfunction was assessed using ectopic expression and depletion experiments. CEBPB, MALAT1 and CIRBP were highly expressed in plasma of SAP patients and pancreatic and intestinal tissues of SAP mice. Further analysis showed that knockdown of MALAT1 could alleviate pancreatic and intestinal injury, reduce inflammation, and prevent gastrointestinal motility dysfunction in SAP mice. The transcription factor CEBPB could bind to the promoter region of MALAT1, thus activating the transcription of MALAT1. MALAT1 interacted with CIRBP and inhibited the degradation of CIRBP, leading to activated extracellular signal-regulated kinase (ERK) pathway and the resultant gastrointestinal motility dysfunction. In conclusion, CEBPB exhibits a promoting activity towards gastrointestinal motility dysfunction in SAP by pumping up MALAT1 expression and activating the CIRBP-dependent ERK pathway.

MALAT1 promotes malignant pleural mesothelioma by sponging miR-141-3p.

The aim of this study was to clarify the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in proliferation, migration, and invasion of malignant pleural mesothelioma (MPM) cells. The quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression of MALAT1 in MPM cell lines. The effects of MALAT1 and miR-141-3p on the proliferation, migration, and invasion of MPM cells were studied through a series of in vitro cellular experiments. The flow cytometry was utilized to detect the cell apoptosis. The dual‐luciferase reporter assay was employed to explore the binding relationship among MALAT1, miR-141-3p, and YES-associated protein 1 (YAP1). MALAT1 was overexpressed in MPM cell lines, while its knockdown significantly inhibited the cell proliferation, migration, and invasion, and increased the number of MPM cells in the G0/G1 phase. In addition, MALAT1 could directly bind to miR-141-3p and inhibit its expression. YAP1 has been identified as a downstream target of miR-141-3p, and its expression level was inhibited by miR-141-3p. MALAT1 can be used as a competitive endogenous RNA (ceRNA) to regulate the YAP1-Hippo signaling pathway through miR-141-3p, promote the proliferation, migration, and invasion of MPM cells, and provide a new target for the therapy of MPM.

Long Noncoding RNA MALAT1 Interacts with miR-124-3p to Modulate Osteosarcoma Progression by Targeting SphK1.

Introduction Long noncoding RNAs (lncRNAs) have been implicated in a variety of biological functions, including tumor proliferation, apoptosis, progression, and metastasis. lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overexpressed in various cancers, as well as osteosarcoma (OS); however, its underlying mechanism in OS is poorly understood. This investigation aims to elucidate the mechanisms of MALAT1 in OS proliferation and migration and to provide theoretical grounding for further targeted therapy in OS. Methods In the present study, we applied qRT-PCR to assess the MALAT1 expression in OS tissues and cell lines. The effects of MALAT1 and miR-124-3p on OS cell proliferation and migration were studied by CCK-8 and scratch assays. Cell cycle and apoptosis were tested using a flow cytometer. The competing relationship between MALAT1 and miR-124-3p was confirmed by dual-luciferase reporter assay. Results MALAT1 was overexpressed in OS cell lines and tissue specimens, and knockdown of MALAT1 significantly inhibited cell proliferation and migration and increased cell apoptosis and the percentage of G0/G1 phase. Furthermore, MALAT1 could directly bind to miR-124-3p and inhibit miR-124-3p expression. Moreover, MALAT1 overexpression significantly relieved the inhibition on OS cell proliferation mediated by miR-124-3p overexpression, which involved the derepression of sphingosine kinase 1 (SphK1). Conclusions We propose that lncRNA MALAT1 interacts with miR-124-3p to modulate OS progression by targeting SphK1. Hence, we identified a novel MALAT1/miR-124-3p/SphK1 signaling pathway in the regulation of OS biological behaviors.

Long non-coding RNA MALAT1 regulates oxaliplatin-resistance via miR-324-3p/ADAM17 axis in colorectal cancer cells

BackgroundColorectal cancer (CRC) is one of the most general malignant tumors. Accumulating evidence implied that long non-coding RNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) participated in the tumorigenesis of CRC. However, the effect of MALAT1 in drug-resistance needed to be further illustrated.MethodsLevels of MALAT1, microRNA (miR)-324-3p, and a disintegrin and metalloprotease metallopeptidase domain 17 (ADAM17) were detected using quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Cell Counting Kit 8 (CCK-8) was used to assess the half maximal inhibitory concentration (IC50) of oxaliplatin (Ox). Meanwhile, cell proliferation, migration and apoptosis were detected by CCK-8, transwell assay, and flow cytometry, respectively. The interaction between miR-324-3p and MALAT1 or ADAM17 was clarified by dual-luciferase reporter assay. Also, the effect of MALAT1 on tumor growth was detected in xenograft tumor mice treated with Ox.ResultsSignificant up regulation of MALAT1 and ADAM17, and decrease of miR-324-3p were observed in Ox-resistant CRC tissues and cells. MALAT1 deficiency enhanced the sensitivity of Ox-resistant CRC cells response to Ox, while miR-324-3p repression or ADAM17 acceleration could overturn this effect. Moreover, MALAT1 silencing repressed tumor growth in Ox-treated nude mice. Mechanically, MALAT1 exerted promotion effect on the resistance response to Ox via miR-324-3p/ADAM17 axis in Ox-resistant CRC cells.ConclusionMALAT1 modulated the sensitivity of Ox through ADAM17 in Ox-resistant CRC cells by sponging miR-324-3p, thus MALAT1 might serve as a novel insight for the therapy of CRC.

MiR-146b-5p Regulates the Expression of Long Noncoding RNA MALAT1 and Its Effect on the Invasion and Proliferation of Papillary Thyroid Cancer.

Background: The incidence of thyroid cancer has increased dramatically in recent decades due, in large part, to identifications of subclinical diseases. Literature on thyroid cancer has examined the pathogenesis of high invasive papillary thyroid cancer (PTC) and has improved the prevention and treatment of PTC. This study aims to investigate the effects of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on PTC migration and invasion, and clarify the regulatory mechanisms between miR-146b-5p and MALAT1. Materials and Methods: In this study, we examined the differential expression of MALAT1, miR-146b-5p, and DNA methyltransferases 3A (DNMT3A) in PTC tissues. The effect of MALAT1 on the proliferation and invasion ability of PTC cells was verified by constructing a sh-MALAT1 knockdown cell model. Correlations between MALAT1, miR-146b-5p, and DNMT3A were analyzed by the Pearson correlation method. Finally, we verified the regulatory relationship between miR-146b-5p and MALAT1 by the luciferase assay and rescue assay. Results: The expression of MALAT1 was upregulated in PTC tissues and cells, while a MALAT1 knockdown counteracted cellular activity, migration, and invasion of B-CPAP and K1 cells. The relationship between miR-146b-5p and DNMT3A was negative, while the relationship between miR-146b-5p and MALAT1 was positive. Both genes were separately detected using the Pearson correlation method. The luciferase assay and rescue assay demonstrated that a binding site in miR-146b-5p was existent in the 3' untranslated region of DNMT3A, while a knockdown of DNMT3A partially rescued si-miR-146b-5p induced proliferation, migration, and invasion effects on PTC cells. Conclusions: The MALAT1 gene is highly expressed in PTC, while the knockdown MALAT1 gene attenuates the cellular activity and invasive ability of PTC cells. The microRNA miR-146b-5p can promote a MALAT1 expression by negatively regulating DNMT3A in PTC.

The potency of lncRNA MALAT1/miR-155/CTLA4 axis in altering Th1/Th2 balance of asthma.

Objectives: The present study examined if the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/miR-155/CTLA-4 axis was involved in modifying Th1/Th2 balance, a critical indicator for asthma progression. Methods: Altogether 772 asthma patients and 441 healthy controls were recruited, and their blood samples were collected to determine expressional levels of MALAT1, miR-155, CTLA-4, T-bet, GATA3, Th1-type cytokines and Th2-type cytokines. The CD4+ T cells were administered with pcDNA3.1-MALAT1, si-MALAT1, miR-155 mimic and miR-155 inhibitor to assess their effects on cytokine release. The luciferase reporter gene assay was also adopted to evaluate the sponging relationships between MALAT1 and miR-155, as well as between miR-155 and CTLA-4. Results: Over-expressed MALAT1 and under-expressed miR-155 were more frequently detected among asthma patients who showed traits of reduced forced expiratory failure volume in 1 s (FEV1), FEV1/forced vital capacity (FVC) and FEV1% of predicted (P<0.05). Moreover, MALAT1 expression was negatively expressed with the Th1/Th2 and T-bet/GATA3 ratios, yet miR-155 expression displayed a positively correlation with the ratios (P<0.05). Additionally, the IFN-γ, IL-2 and T-bet levels were reduced under the influence of pcDNA3.1-MALAT1 and miR-155 inhibitor, while levels of IL-4, IL-10 and GATA3 were raised under identical settings (P<0.05). Furthermore, MALAT1 constrained expression of miR-155 within CD4+ T cells by sponging it, and CTLA-4 could interfere with the effects of MALAT1 and miR-155 on Th1/Th2 balance and T-bet/Gata3 ratio (P<0.05). Conclusion: MALAT1 sponging miR-155 was involved with regulation of Th1/Th2 balance within CD4+ T cells, which might aid to develop therapies for amelioration of asthmatic inflammation.

MALAT1 inhibits the Wnt/β-catenin signaling pathway in colon cancer cells and affects cell proliferation and apoptosis.

Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is a highly conserved long noncoding RNA, which has been related to various pathological processes, including cancer. The role and mechanism of MALAT1 in colon cancer are not clear. We investigated MALAT1 expression in colon cancer tissues, the effect of MALAT1 on proliferation and apoptosis of SW480 cells, and the signaling pathway involved in the MALAT1 effects. MALAT1 expression was determined in 60 colon cancer and para-carcinoma tissues using reverse transcription polymerase chain reaction (RT-PCR). Knockdown of MALAT1 in SW480 cells was induced by small interfering RNA (siRNA), and the cells were divided into three groups: untreated control, nonsense siRNA-treated control, and MALAT1 siRNA-treated group. SW480 cell apoptosis was assessed using TUNEL assay and flow cytometry. Apoptosis-related and Wnt/β-catenin signaling pathway-related proteins were detected by Western blotting in SW480 cells. SW480 cell proliferation was assessed by CCK-8 assay. MALAT1 expression was significantly higher in colon cancer vs. para-carcinoma tissues. Knockdown of MALAT1 by siRNA increased the number of apoptotic cells and the apoptosis rate at 24 h post-transfection in SW480 cells. Bcl2 associated X protein (Bax) expression was increased, B-cell lymphoma 2 (Bcl-2) expression was decreased, and the ratio of cleaved caspase-3 to truncated caspase-3 was increased in MALAT1 siRNA-transfected SW480 cells. MALAT1 knockdown decreased the proliferation of SW480 cells at 24 h, 48 h, and 72 h post-transfection. Wnt and β-catenin expression was inhibited in MALAT1 siRNA-transfected SW480 cells. Inhibition of MALAT1 expression in colon cancer may promote apoptosis and hinder cell proliferation by suppressing the activation of Wnt/β-catenin signaling pathway.

Effect of MALAT1 in the crosstalk between nucleus and mitochondria on mitochondrial reprogramming in hepatocellular carcinoma cells.

e14711 Background: Mitochondria-nuclear crosstalk is a bidirectional pathway of communication between mitochondria and nucleus that influences many cellular and organismal activities. This crosstalk can regulate several oncogenic pathways involved in tumorigenesis. MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), a nucleus-encoded lncRNA, dysregulated in multiple human malignancies is recently found to drive mitochondria dysfunction in Mitochondria-nuclear crosstalk. Methods: RNA sequencing, “RNA reverse transcription-associated trap sequencing” (RAT-seq), RNA immunoprecipitation(RIP), fluorescence in situ hybridization (FISH), were performed to detect the position of the MALAT1, and its interaction protein and DNAs in HepG2 cell line. After silencing MALAT1 by shRNAs, Seahorse, ATP production, lysotracker staining, Western blot, and electronic microscope were used to measure metabolism, ROS amount, mitophagy, apoptosis and mitochondrial morphology of the silencing cell lines. Results: By combining mitochondrial RNA-Seq with FISH, it is surprised to discover that MALAT1 was enriched in the mitochondria of HepG2 cells. Using RAT-seq approach, MALAT1 was found to utilized it 3’-fragment to interact with multiple loci of mitochondrial DNA( D-loop, COX2, ND3, and CYTB ). The RIP and affinity RNA pulldown assays suggested that the RNA-binding protein HuR mediated the transportation of MALAT1 to the mitochondria. Also, mitochondria transmembrane protein mitochondrial carrier 2(MTCH2) is found to interacted MALAT1, suggesting that MALAT1 may through the MTCH2 to get into the inside of the mitochondria. Knockdown of MALAT1 induced multiple abnormalities in mitochondrial functions, including low OXPHOS, low ATP production, reduced mitophagy, declined mtDNA copy number, and activation of the mitochondrial apoptosis pathway. Conclusions: Together, this study greatly expands our knowledge of the nucleus-encoded lncRNA MALAT1 driving the mitochondria dysfunction. Our study establishes MALAT1 as a regulator through interacting with MT-DNA, HuR, MTCH2 protein, revealing a new regulatory mechanism of mitochondria. Many novel nucleus-encoded RNAs existing in mitochondria were identified at the first time, suggesting novel biological functions of lncRNAs, laying the foundation for further clarifying their roles.

Long Noncoding RNA MALAT1 Regulates Cancer Glucose Metabolism by Enhancing mTOR-Mediated Translation of TCF7L2.

Reprogrammed glucose metabolism of enhanced aerobic glycolysis (or the Warburg effect) is known as a hallmark of cancer. The roles of long noncoding RNAs (lncRNA) in regulating cancer metabolism at the level of both glycolysis and gluconeogenesis are mostly unknown. We previously showed that lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) acts as a proto-oncogene in hepatocellular carcinoma (HCC). Here, we investigated the role of MALAT1 in regulating cancer glucose metabolism. MALAT1 upregulated the expression of glycolytic genes and downregulated gluconeogenic enzymes by enhancing the translation of the metabolic transcription factor TCF7L2. MALAT1-enhanced TCF7L2 translation was mediated by upregulation of SRSF1 and activation of the mTORC1-4EBP1 axis. Pharmacological or genetic inhibition of mTOR and Raptor or expression of a hypophosphorylated mutant version of eIF4E-binding protein (4EBP1) resulted in decreased expression of TCF7L2. MALAT1 expression regulated TCF7L2 mRNA association with heavy polysomes, probably through the TCF7L2 5'-untranslated region (UTR), as determined by polysome fractionation and 5'UTR-reporter assays. Knockdown of TCF7L2 in MALAT1-overexpressing cells and HCC cell lines affected their metabolism and abolished their tumorigenic potential, suggesting that the effects of MALAT1 on glucose metabolism are essential for its oncogenic activity. Taken together, our findings suggest that MALAT1 contributes to HCC development and tumor progression by reprogramming tumor glucose metabolism. SIGNIFICANCE: These findings show that lncRNA MALAT1 contributes to HCC development by regulating cancer glucose metabolism, enhancing glycolysis, and inhibiting gluconeogenesis via elevated translation of the transcription factor TCF7L2.

Long noncoding RNA MALAT1 regulates sepsis in patients with burns by modulating miR‑214 with TLR5.

The present study aimed to identify the involvement of the dysregulation of the metastasis‑associated lung adenocarcinoma transcript‑1 (MALAT1)/microRNA (miR)‑214/Toll‑like receptor (TLR)5 signaling pathway in the development of post‑burn sepsis. THP‑1 cells were used in the present study, in addition to 8‑10week‑old mice. ELISA analysis was performed to examine the expression levels of inflammation‑associated factors. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis and western blotting were performed to analyze the influence of burns or burns with infection on the production of MALAT1, miR‑214 and TLR5. Commonly‑used software and a luciferase assay was used to confirm the target gene of miR‑214. RT‑qPCR analysis and western blotting were performed to elucidate the effects of lipopolysaccharide (LPS), miR‑214 and MALAT1 on the expression of miR‑214, TLR5, tumor necrosis factor (TNF)‑α, interleukin (IL)‑6 and IL‑10. Burn injury increased TLR5, TNF‑α, IL‑6 and IL‑10 expression levels, which were abolished by treatment with MALAT1. miR‑214 directly targeted TLR5 by binding to the TLR5 3' untranslated region (ITR), and the luciferase activity of the wild‑type, and not the mutant, TLR5 3'UTR was reduced following transfection with miR‑214. In cells not treated with LPS, MALAT1 and anti‑miR‑214 significantly enhanced TLR5, TNF‑α, IL‑6 and IL‑10 expression, and repressed miR‑214 production; whereas, miR‑214 and MALAT1 short hairpin (sh)RNA decreased TLR5, TNF‑α, IL‑6 and IL‑10 expression levels, and increased miR‑214 expression. In cells treated with LPS, LPS reduced miR‑214 expression and increased TLR5, TNF‑α, IL‑6 and IL‑10 expression compared with LPS‑untreated cells, and the effects of MALAT1, anti‑miR‑214, miR‑214 and MALAT1 shRNA on TLR5, TNF‑α, IL‑6 and IL‑10 were the same as in LPS‑untreated cell. The results of the present study indicated the association between the dysregulation of MALAT1/miR‑214/TLR5 and the risk of post‑burn sepsis.

LncRNA MALAT1/MiR-145 Adjusts IL-1β-Induced Chondrocytes Viability and Cartilage Matrix Degradation by Regulating ADAMTS5 in Human Osteoarthritis.

PurposeAccumulating evidence suggests that microRNA-145 (miR-145) plays an important role in osteoarthritis (OA), which is a chronic progressive joint disease. Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) promotes metastasis in cancers and functions as a sponge for miR-145. However, the role of MALAT1/miR-145 in OA pathogenesis has not yet been elucidated.Materials and MethodsThe expression of MALAT1 and miR-145 was examined by quantitative real-time PCR; the interaction between miR-145, MALAT1 and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 5 was verified by luciferase reporter assay. Correlations among MALAT1, miR-145, and ADAMTS5 were analyzed by Spearman rank analysis. Chondrocytes viability and cartilage extracellular matrix (ECM) degradation were investigated with cell viability assay and Western blotting analyzing expression of ADAMTS5, collagen type 2 alpha 1 (COL2A1), aggrecan (ACAN), and cartilage oligomeric matrix protein (COMP).ResultsMALAT1 was upregulated, and miR-145 was downregulated in OA samples and IL-1β-induced chondrocytes. Mechanically, miR-145 could directly bind to MALAT1 and ADAMTS5. Moreover, miR-145 expression was negatively correlated with MALAT1 and ADAMTS5 expression in OA patients, whereas MALAT1 and ADAMTS5 expression was positively correlated. Functionally, overexpression of MALAT1 inhibited chondrocyte viability and promoted cartilage ECM degradation in IL-1β-induced chondrocytes. In support thereof, MALAT1 silencing and miR-145 upregulation exerted the opposite effect in IL-1β-induced chondrocytes. Moreover, the effect of MALAT1 was counteracted by miR-145 upregulation, and ADAMTS5 restoration could abate miR-145 effects.ConclusionAn MALAT1/miR-145 axis contributes to ECM degradation in IL-1β-induced chondrocytes through targeting ADAMTS5, suggesting that MALAT1/miR-145/ADAMTS5 signaling may underlie human OA pathogenesis.

LncRNA MALAT1 protects cardiomyocytes from isoproterenol-induced apoptosis through sponging miR-558 to enhance ULK1-mediated protective autophagy.

Investigating the molecular mechanisms of myocardial infarction (MI) and subsequent heart failure have gained considerable attention worldwide. Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been previously demonstrated to regulate the proliferation and metastasis of several tumors. However, little is known about the effects of MALAT1 in MI and in regulating the cell date after MI. In our study, first, it was shown that the expression levels of MALAT1 were increased in the MI samples compared with normal tissues using quantitative reverse-transcription polymerase chain reaction. Then, MALAT1 knockdown could significantly decrease the cell viability and increase the apoptotic rates in isoproterenol (ISO)-treated H9C2 cells. In addition, we screened the possible target and found that miR-558 is its direct target using dual luciferase reporter assay, indicating that MALAT1 functioned as decoys sponging miR-558. Transfection of miR-558 mimic decreased the cell viability and enhanced the apoptosis. Furthermore, we revealed that miR-558 could downregulate ULK1 expression and suppressed ISO-induced protective autophagy. Activation of MALAT1/miR-558/ULK1 pathway protected H9C2 cells from ISO-induced mitochondria-dependent apoptosis. Finally, we used MALAT1-knockout mice to further demonstrated that MALAT1 protected cardiomyocytes from apoptosis and partially improved the cardiac functions upon ISO treatment. In conclusion, we elucidated that lncRNA MALAT1 protected cardiomyocytes from ISO-induced apoptosis by sponging miR-558 thus promoting ULK1-dependent autophagy. Targeting lncRNA MALAT1 might become a potential strategy in protecting cardiomyocytes during MI.

Long non-coding RNA MALAT1 acts as a competing endogenous RNA to promote malignant melanoma growth and metastasis by sponging miR-22.

Long non-coding RNAs (lncRNAs) are involved in tumorigenesis. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), an lncRNAs, is associated with the growth and metastasis of many human tumors, but its biological roles in malignant melanoma remain unclear. In this study, the aberrant up-regulation of MALAT1 was detected in melanoma. We determined that MALAT1 promotes melanoma cells proliferation, invasion and migration by sponging miR-22. MiR-22 was decreased and acted as a tumor suppressor in melanoma, and MMP14 and Snail were the functional targets of miR-22. Furthermore, MALAT1 could modulate MMP14 and Snail by operating as a competing endogenous RNA (ceRNA) for miR-22. The effects of MALAT1 in malignant melanoma is verified using a xenograft model. This finding elucidates a new mechanism for MALAT1 in melanoma development and provides a potential target for melanoma therapeutic intervention.

MALAT1 promotes the proliferation and invasion of thyroid cancer cells via regulating the expression of IQGAP1.

Increasing evidence indicated that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) acted as a key regulator in the proliferation and invasion of several cancers. However, the function of MALAT1 in the development of thyroid cancer has not been experimentally established. The expression of MALAT1 and IQGAP1 in thyroid cancer tissues and cells were detected by quantitative real-time PCR and western blot. The effects of MALAT1 and IQGAP1 on the cell proliferation and invasion of thyroid cancer cells were detected with a 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium 4 (MTT) assay and a Transwell assay, respectively. FTC-133 or SW1736 transfected with si-MALAT1 or pcDNA-MALAT1 were injected subcutaneously into 4-week-olds BALB/c mice to examine the impact of MALAT1 on the tumor development of thyroid cancer in vivo. In this study, we discovered the higher level of MALAT-1 and expression of IQGAP1 in thyroid cancer tissues and in thyroid cancer cells compared to that in the control. MTT and Transwell assay showed that the proliferation and invasion of FTC-133 cells with MALAT-1 knockdown were inhibited. Moreover, MALAT-1 could upregulate the expression of IQGAP1 in thyroid cancer cells. In addition, IQGAP1 knockdown reversed the decreasing cell proliferation and invasion of thyroid cancer induced by MALAT-1 overexpression. Finally, the study in vivo verified that MALAT-1 promoted the tumor growth of thyroid cancer. Our study indicated that MALAT1 promoted the proliferation and invasion of thyroid cancer cells via regulating the expression of IQGAP1.

The role of MALAT1 correlates with HPV in cervical cancer.

Cervical cancer, the second most common type of cancer in women worldwide, is responsible for >275,100 mortalities each year and is associated with high-risk human papilloma virus (HR-HPV). HPVs have two important oncogenes, E6 and E7, which have crucial roles in malignant transformation in cervical cancer. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA originally identified in non-small cell lung cancer. Previous studies have revealed that MALAT1 is expressed in numerous tissue types, and is significant in maintaining the normal function of the body. However, it also appeared to be notably upregulated in numerous carcinoma types compared with adjacent non-cancerous tissues. In the present study, it was identified that MALAT1 expression was upregulated in cervical cancer cell lines compared with normal cervical squamous cell samples. Further study into the effect of MALAT1 on cellular phenotype revealed that MALAT1 was able to promote cell migration and proliferation. Of note, it was revealed that the expression of MALAT1 was decreased with the knockdown of HPV16 E6/E7 in CaSki cells. Furthermore, the investigations in clinical samples also revealed that MALAT1 was expressed in HPV-positive cervical squamous cells, but not in HPV-negative normal cervical squamous cells. These results indicate that HPV correlates with MALAT1 deregulation in cervical cancer.