Myocardial Infarction Associated Transcript Knockdown Research Articles

Long noncoding RNA MIAT regulates TP53 ubiquitination and expedites prostate adenocarcinoma progression by recruiting TBL1X.

Despite recent advances in cancer immunotherapy, their efficacy for treating patients with prostate adenocarcinoma (PRAD) is low due to complex immune evasion mechanisms. However, the function of long non-coding RNA (lncRNAs) in immune evasion has not been fully clarified. This study aimed to expound the role of myocardial infarction-associated transcript (MIAT), a lncRNA significantly upregulated in three PRAD-associated datasets, in immune evasion and try to reveal the potential mechanism. MIAT was highly expressed in PRAD tissues and predicted poor prognosis, and suppression of MIAT inhibited the malignant biological behavior of PRAD cells. Moreover, the depletion of MIAT promoted the immune response of CD8+ T cells and hampered the immune evasion of PRAD cells. In addition, MIAT downregulated TP53 protein expression by recruiting transducin beta-like protein 1X (TBL1X) for ubiquitination modification. Silencing of TP53 or overexpression of TBL1X was enough to abate the tumor suppressive effects of MIAT knockdown in vitro and in vivo. Our results provide evidence for a novel regulation mechanism of CD8+ T cells in PRAD and MIAT may serve as a potential therapeutic target in PRAD.

Investigation into the Role of Long-Non-Coding RNA MIAT in Leukemia.

Myocardial Infarction Associated Transcript (MIAT) is a nuclear long non-coding RNA (LncRNA) with four different splicing variants. MIAT dysregulation is associated with carcinogenesis, mainly acting as an oncogene regulating cellular growth, invasion, and metastasis. The aim of the current study is to investigate the role of MIAT in the regulation of T and chronic myeloid leukemic cell survival. To this end, MIAT was silenced using MIAT-specific siRNAs in leukemic cell lines, and functional assays were performed thereafter. This investigation also aims to investigate the effects of MIAT silencing on the expression of core genes involved in cancer. Functional studies and gene expression determination confirm that MIAT knockdown not only affects short- and long-term survival and the apoptosis of leukemic cells but also plays a pivotal role in the alteration of key genes involved in cancer, including c-MYC and HIF-1A. Our observations suggest that MIAT could act as an oncogene and it has the potential to be used not only as a reliable biomarker for leukemia, but also be employed for prognostic and therapeutic purposes.

LncRNA MIAT Upregulates NEGR1 by Competing for miR-150-5p as a Competitive Endogenous RNA in SCIRI Rats.

Spinal cord ischemia-reperfusion injury (SCIRI) can cause a pathological state of irreversible delayed death of neurons in the spinal cord tissue and a range of complications, such as spinal cord dysfunction and motor function impairment. This study aimed to determine whether the long-stranded non-coding ribonucleic acid (lncRNA), myocardial infarction-associated transcript (MIAT), could upregulate neuronal growth regulator 1 (NEGR1) by competing for miR-150-5p as a competitive endogenous RNA in a rat SCIRI model. The MIAT knockdown vector or the corresponding blank vector was injected into the spinal cord of healthy sprague Dawley (SD) rats. Administration of the MIAT knockdown vector led to the establishment of the SCIRI rat model. Basso, Beattie & Bresnahan locomotor rating scale (BBB) assessment of hind limb motion. Pathological changes in the spinal cord were observed via hematoxylin and eosin staining and eosin staining. Quantitative polymerase chain reaction was performed to determine the expression levels of the candidate microRNAs and predicted candidate genes, and the relationship between them. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining was used to detect apoptosis in the spinal cord tissue of rats in each group. Western blotting was performed to determine the expression of the apoptosis-related proteins, caspase-9, caspase-3, and BCL2-Associated X (Bax)/B-cell lymphoma-2 (Bcl-2). The luciferase reporter gene was used to assess the interaction among the lncRNA, MIAT, and miR-150-5, and the interaction between miR-150-5 and NEGR1. The sh-lncRNA, MIAT, improved exercise status, and pathological changes in the spinal cord of SCIRI rats, inhibited apoptosis, increased the expression of miR-150-5p, and reduced the expression of NEGR1. Compared with mimics-NC, the transfection of miR-150-5p significantly decreased the relative fluorescence activity ratio of MIAT 3'-untranslated region (3'-UTR) wild-type Human embryonic kidney cells 293 (HEK-293 cells). Compared with mimics-negative control (NC), the transfection of miR-150-5p significantly decreased the relative fluorescence activity ratio of NEGR1 3'-UTR wild-type HEK-293 cells. MIAT can affect the symptoms of SCIRI in rats. Furthermore, as a competitive endogenous RNA, MIAT upregulates NEGR1 by competing with miR-150-5p in SCIRI rats.

Knockdown of long noncoding RNA MIAT attenuates hypoxia-induced cardiomyocyte injury by regulating the miR-488-3p/Wnt/β-catenin pathway.

Dysfunction of cardiomyocytes contributes to the development of acute myocardial infarction (AMI). Nonetheless, the regulatory mechanism of lncRNA myocardial infarction-associated transcript (MIAT) in cardiomyocyte injury remains largely unclear. The cardiomyocyte injury was assessed via cell viability and apoptosis using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and flow cytometry, respectively. The levels of MIAT, microRNA (miR)-488-3p, and Wnt5a were detected via quantitative real-time polymerase chain reaction and Western blot. After bioinformatical analysis, the binding between miR-488-3p and MIAT or Wnt5a was confirmed via dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. Our results showed that MIAT expression was increased in AC16 cells after hypoxia treatment. Silencing of MIAT alleviated hypoxia-induced viability reduction, apoptosis increase, and Wnt/β-catenin pathway activation. MIAT directly targeted miR-488-3p. MiR-488-3p might repress hypoxia-induced cardiomyocyte injury, and its knockdown reversed the effect of MIAT depletion on cardiomyocyte injury. Wnt5a was validated as a target of miR-488-3p. Wnt5a expression restoration attenuated the influence of MIAT knockdown on hypoxia-triggered cardiomyocyte injury. Our findings demonstrated that downregulation of MIAT might mitigate hypoxia-induced cardiomyocyte injury partly through miR-488-3p mediated Wnt/β-catenin pathway.

Knockdown of long noncoding RNA MIAT attenuates cigarette smoke-induced airway remodeling by downregulating miR-29c-3p–HIF3A axis

Chronic obstructive pulmonary disease (COPD) is a global public health issue and is defined as persistent airflow limitation. COPD is a major cause of morbidity and mortality worldwide. Long noncoding RNAs are involved in the course of pulmonary diseases. Here, we revealed that a long noncoding RNA called myocardial-infarction–associated transcript (MIAT) is upregulated in lung tissues of cigarette smoke (CS)-exposed mice. Knockdown of MIAT attenuated CS or CS-extract–induced inflammatory processes, epithelial-mesenchymal transition (EMT), and collagen deposition. Moreover, according to bioinformatic analyses and luciferase reporter assays, MIAT binds to microRNA-29c-3p (miR-29c-3p) and upregulates hypoxia-inducible factor 3 alpha (HIF3A), a target gene of miR-29c-3p. When the MIAT-specific short hairpin RNA and an miR-29c-3p inhibitor were cotransfected into cells, the inhibitor reversed the effects of MIAT knockdown on cell proliferation, apoptosis, inflammation, EMT, and collagen deposition. Overall, these results indicate that MIAT participates in CS-induced EMT and airway remodeling in COPD by upregulating miR-29c-3p–HIF3A axis output, thereby offering a novel promising biomarker for the assessment of COPD exacerbation induced by CS exposure.

LncRNA MIAT enhances cerebral ischaemia/reperfusion injury in rat model via interacting with EGLN2 and reduces its ubiquitin-mediated degradation.

Long non‐coding RNA (lncRNA) MIAT (myocardial infarction associated transcript) has been characterized as a functional lncRNA modulating cerebral ischaemic/reperfusion (I/R) injury. However, the underlying mechanisms remain poorly understood. This study explored the functional partners of MIAT in primary rat neurons and their regulation on I/R injury. Sprague‐Dawley rats were used to construct middle cerebral artery occlusion (MCAO) models. Their cerebral cortical neurons were used for in vitro oxygen‐glucose deprivation/reoxygenation (OGD/R) models. Results showed that MIAT interacted with EGLN2 in rat cortical neurons. MIAT overexpression or knockdown did not alter EGLN2 transcription. In contrast, MIAT overexpression increased EGLN2 stability after I/R injury via reducing its ubiquitin‐mediated degradation. EGLN2 was a substrate of MDM2, a ubiquitin E3 ligase. MDM2 interacted with the N‐terminal of EGLN2 and mediated its K48‐linked poly‐ubiquitination, thereby facilitating its proteasomal degradation. MIAT knockdown enhanced the interaction and reduced EGLN2 stability. MIAT overexpression enhanced infarct volume and induced a higher ratio of neuronal apoptosis. EGLN2 knockdown significantly reversed the injury. MIAT overexpression reduced oxidative pentose phosphate pathway flux and increased oxidized/reduced glutathione ratio, the effects of which were abrogated by EGLN2 knockdown. In conclusion, MIAT might act as a stabilizer of EGLN2 via reducing MDM2 mediated K48 poly‐ubiquitination. MIAT‐EGLN2 axis exacerbates I/R injury via altering redox homeostasis in neurons.

Downregulation of MIAT reduces the proliferation and migratory and invasive abilities of retinoblastoma cells by sponging miR-665 and regulating LASP1.

Long non-coding RNAs (lncRNAs) can function as onco-lncRNAs in several types of human cancer, including retinoblastoma (Rb). The present study investigated the potential role and regulatory mechanism of the lncRNA myocardial infarction-associated transcript (MIAT) in Rb. To do so, the expression levels of MIAT, microRNA (miR)-665, and LIM and SH3 protein 1 (LASP1) in Rb tissues from patients or Rb cells were analysed using reverse transcription quantitative PCR. The interactions between miR-665 and MIAT/LASP1 were confirmed by the dual-luciferase reporter assay. MTT, Transwell (to assess migration and invasion) and western blotting assays were used to explore the functions of the MIAT/miR-665/LASP1 axis on Rb progression in vitro. The results of the present study indicated that MIAT targeted miR-665. In Rb tissues and cell lines, high expression of MIAT was observed, whereas miR-665 was downregulated in Rb tissues. Furthermore, the proliferation and migratory and invasive abilities of Rb Y79 and HXO-RB44 cells were decreased following MIAT downregulation or miR-665 overexpression. In addition, LASP1 was identified as a target gene of miR-665. Both the decreased expression of miR-665 and the elevated expression of LASP1 reversed the suppressive effects of MIAT knockdown on the proliferation and migratory and invasive abilities of Y79 cells. Furthermore, MIAT silencing attenuated the development of Rb by regulating the miR-665/LASP1 axis. Taken together, these findings suggested that MIAT may be considered as a possible therapeutic target for Rb.

LncRNA MIAT knockdown alleviates oxygen-glucose deprivation‑induced cardiomyocyte injury by regulating JAK2/STAT3 pathway via miR-181a-5p

BackgroundCoronary artery disease (CAD) is a common heart disease with high incidence and mortality. Myocardial ischemia is the main type of CAD, which negatively affects health worldwide. The aim of the present study was to investigate the function and mechanism of myocardial infarction-associated transcript (MIAT) in myocardial ischemia. MethodsHuman cardiomyocytes (HCM) were treated with oxygen-glucose deprivation (OGD) to set the in vitro model and mouse myocardial ischemia/reperfusion (I/R) was set for in vivo model. Cell viability and apoptosis were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, flow cytometry, and immunofluorescence analysis. Inflammatory cytokines levels were detected by enzyme-linked immunosorbent assay. Gene and protein expressions were identified by quantitative real time-polymerase chain reaction or Western blotting. The interaction of MIAT, miR-181a-5p, and janus kinase 2 (JAK2) was identified by dual-luciferase report assay. Mouse heart tissues histopathological condition were observed by hematoxylin and eosin assays. ResultsExpression of MIAT and JAK2 were increased in OGD-treated HCM and mice of I/R model group, and miR-181a-5p was decreased. MIAT silencing could reverse the OGD treatment induced cell proliferation inhibition, cleaved caspase-3 and Bcl2-associated X (Bax) levels increased, while those of B-cell lymphoma-2 (Bcl-2) and mitochondria's cyt-C decreased. Besides, MIAT knockdown attenuated the OGD-induced increase of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 levels. Moreover, MIAT targeted miR-181a-5p to enhance the expression of JAK2 and signal Transducer and Activator of Transcription 3 (STAT3), and miR-181a-5p overexpression promoted proliferation, whereas it inhibited apoptosis in OGD-induced cardiomyocytes. Furthermore, the regulatory effects of MIAT knockdown in cell proliferation, apoptosis, and inflammatory injury was reversed by inhibition of miR-181a-5p or overexpression of JAK2 in OGD-treated HCM. Knockdown of MIAT reduced myocardial injury caused by I/R treatment in vivo. ConclusionMIAT knockdown inhibited apoptosis and inflammation by regulating JAK2/STAT3 signaling pathway via targeting miR-181a-5p in myocardial ischemia model. MIAT can be a possible therapeutic target for controlling the progression of myocardial ischemia.

LncRNA MIAT Mediates ox-LDL-Induced Endothelial Cell Injury Via miR-206/RAB22A Axis

BackgroundLong non-coding RNA myocardial infarction associated transcript (MIAT) has exerted significant effects on atherosclerosis (AS). The biological roles of MIAT in endothelial cell dysfunction are not thoroughly elucidated. MethodsThe expression of MIAT, microRNA (miR)-206 and Ras-related protein Rab-22A (RAB22A) was detected by quantitative real-time polymerase chain reaction and western blot. The injury of human umbilical vein endothelial cells (HUVECs) was evaluated by testing cell viability, invasion, migration, apoptosis, epithelial-mesenchymal transition capacities and inflammatory response using cell counting kit-8, transwell, wound healing assays, flow cytometry, western blot and enzyme-linked immunosorbent assay, respectively. The binding interaction between miR-206 and MIAT or RAB22A was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. ResultsThe expression of MIAT was up-regulated in ox-LDL-treated HUVECs, and knockdown of MIAT in ox-LDL-treated HUVECs remarkably promoted cell viability, invasion, migration, and epithelial-mesenchymal transition (EMT), as well as suppressed cell apoptosis and the levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and endothelial nitric oxide synthase (eNOS). In a mechanical study, MIAT directly targeted miR-206, and miR-206 inhibition attenuated the protective effects of MIAT knockdown on ox-LDL-triggered HUVEC injury. Besides that, RAB22A was a target of miR-206, and RAB22A overexpression reversed the biological effects of miR-206 on ox-LDL-treated HUVECs. Additionally, we also proved MIAT could regulate RAB22A via miR-206 in HUVECs. ConclusionMIAT knockdown impaired ox-LDL-induced HUVEC injury via regulating miR-206/RAB22A axis, suggesting the potential impacts of MIAT on AS occurrence, which revealed a potential therapeutic strategy for future clinic intervention in AS.

Long Non-coding RNA MIAT Knockdown Prevents the Formation of Intracranial Aneurysm by Downregulating ENC1 via MYC.

Intracranial aneurysm (IA) is vascular enlargement occurred on the wall of cerebral vessels and can result in fatal subarachnoid hemorrhage when ruptured. Recent studies have supported the important role of long non-coding RNAs (lncRNAs) in IA treatment. This study identified functional significance of lncRNA myocardial infarction associated transcript (MIAT) in IA. Myocardial infarction associated transcript and ectodermal-neural cortex 1 (ENC1) expression was detected by reverse transcription quantitative polymerase chain reaction. Cell counting kit 8 assay flow cytometry were conducted to detect cell viability and apoptosis of endothelial cells in IA. The interaction among MIAT, ENC1, and myelocytomatosis oncogene (MYC) was analyzed by RNA pull down, RNA immunoprecipitation assay, chromatin immunoprecipitation assay, and dual luciferase reporter assay. Intracranial aneurysm was induced by ligating the left carotid artery and the bilateral posterior branch of the renal artery in rats for studying the role of MIAT and ENC1 in vivo. Myocardial infarction associated transcript and ENC1 were upregulated in IA. Endothelial cells in IA presented a decreased cell viability and an increased apoptotic rate. Myocardial infarction associated transcript could regulate the expression of ENC1, and MYC could bind to the promoter region of ENC1. High expression of MIAT increased endothelial cell apoptosis and vascular endothelial injury, while MIAT knockdown was identified to reduce the risk of IA both in vitro and in vivo through regulating ENC1. To sum up, MIAT silencing is preventive for IA occurrence by decreasing the MYC-mediated ENC1 expression, which represents a novel therapeutic target for IA.

Long Noncoding RNA MIAT Regulates the Process of Laryngeal Squamous Cell Carcinoma Through Regulation of miR-147a/BCOR

Myocardial infarction associated transcript (MIAT) is a long non-coding RNA (lncRNA) that can play oncogenic role in different kinds of cancers. However, its role in laryngeal squamous cell carcinoma (LSCC) remains unknown. The study aimed to explore the effect of MIAT/miR-147a/BCOR axis on LSCC progression. The expression pattern of MIAT, miR-147a and BCOR in LSCC samples and cells was identified through qRT-PCR. The proliferation of LSCC cells was assessed by colony formation assay and CCK-8 assays. Transwell assays were implemented to test the migratory and invasive abilities of LSCC cells. Proteins associated with migration and epithelial-mesenchymal transition were probed in transfected LSCC cells by western blot. The interaction of miR-147a with MIAT or BCOR was analyzed by luciferase reporter assays, RNA pulls down assays and Ago2-RIP assays. High MIAT expression was closely correlated with unfavorable prognosis. MIAT knockdown inhibited cell proliferation, migration, invasion and EMT progress in LSCC. MIAT acted as a miR-147a sponge to increase the expression of BCOR. Silencing of MIAT suppressed LSCC progression through miR-147a/BCOR axis. MIAT acts as an oncogene by controlling miR-147a/BCOR axis in LSCC.

Long non-coding RNA MIAT promotes gastric cancer proliferation and metastasis via modulating the miR-331-3p/RAB5B pathway.

Gastric cancer (GC) remains a threat to the health of the global population. The present study investigated the effects and mechanisms of the long non-coding RNA myocardial infarction associated transcript (MIAT) on the proliferation, apoptosis and metastasis of GC (HGC-27 and AGS) cells. The expression levels of MIAT, micoRNA (miR)-331-3p and RAB5B mRNA were analyzed using reverse transcription-quantitative PCR analysis. Cell growth, apoptosis, migration and invasion were measured using 5-ethynyl-2′-deoxyuridine, flow cytometry, wound healing and Transwell assays, respectively. A luciferase assay was used to determine whether miR-331-3p targeted MIAT and RAB5B. The results indicated that MIAT levels were significantly upregulated in GC tissues and cells, correlated with RAB5B levels and inversely associated with miR-331-3p levels. MIAT overexpression promoted proliferation and metastasis, and inhibited the apoptosis of GC cells. MIAT knockdown had the opposite effect on GC cells. The rescue experiments revealed that the effects of MIAT knockdown on the biological behaviour of GC cells were attenuated by RAB5B overexpression. These data suggest that MIAT promotes GC progression via modulating miR-331-3p/RAB5B pathway.

Long noncoding RNA MIAT regulates primary human retinal pericyte pyroptosis by modulating miR-342–3p targeting of CASP1 in diabetic retinopathy

Diabetic retinopathy (DR) is the leading cause of visual impairment and acquired blindness among adults worldwide. Retinal microvascular pericyte deficiency is one of the earliest pathological changes associated with DR, and long noncoding RNA myocardial infarction-associated transcript (MIAT) has been implicated as a crucial regulator of microvascular dysfunction in DR. Pyroptosis is a caspase-1-dependent proinflammatory form of cell death, and in the present study, we investigated the potential pyroptosis of primary human retinal pericytes (HRPCs) and the mechanism by which MIAT is involved in this process. We applied advanced glycation end product modified bovine serum albumin (AGE-BSA) to simulate the DR environment. The results suggested that AGE-BSA induced the active cleavage of caspase-1 and gasdermin D, the release of IL-1β, IL-18 and LDH, and reduced cell viability, which was prevented by the inhibition of caspase-1, indicating the occurrence of caspase-1-mediated pyroptosis in HRPCs. Immunofluorescence images revealed the phenotypic characteristics of pyroptosis, including pyknosis, swelling and hyperpermeability in plasmolemma. MIAT and CASP1 expression were substantially increased, while that of miR-342–3p was decreased in AGE-BSA-treated HRPCs. MIAT knockdown inhibited pyroptosis in HRPCs, which was reinforced by cotreatment with miR-342–3p mimic but relieved by cotreatment with miR-342–3p inhibitor. Furthermore, HRPC pyroptosis was inhibited by treatment with the miR-342–3p mimic alone but enhanced by the miR-342–3p inhibitor. Luciferase reporter assay results demonstrated binding between MIAT and miR-342–3p, as well as between miR-342–3p and CASP1. MIAT antagonized the effect of miR-342–3p on the depression of its target CASP1 and promoted AGE-BSA-induced pericyte pyroptosis. These findings may promote a better understanding of retinal pericyte depletion pathogenesis and the development of new therapeutic strategies for the treatment of diabetic retinopathy.

Myocardial Infarction-associated Transcript Knockdown Inhibits Cell Proliferation, Migration, and Invasion Through miR-490-3p/Intercellular Adhesion Molecule 1 Axis in Oxidized Low-density Lipoprotein-induced Vascular Smooth Muscle Cells.

Emerging evidence has demonstrated that long noncoding RNAs are related to the pathogenesis of atherosclerosis. We aimed to investigate the roles and molecular mechanisms of myocardial infarction-associated transcript (MIAT) in the proliferation, migration, and invasion of oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs). Quantitative real-time polymerase chain reaction was conducted to determine the levels of MIAT, microRNA490-3p (miR-490-3p), and intercellular adhesion molecule 1 (ICAM1). Cell Counting Kit-8 assay was performed to assess cell proliferation. Transwell assay was used to evaluate cell migration and invasion. Western blot assay was performed to measure the protein levels of proliferating cell nuclear antigen, N-cadherin, matrix metalloprotein-9, and ICAM1. Dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays were conducted to verify the relationship between miR-490-3p and MIAT or ICAM1. MIAT was elevated in atherosclerosis patients' serum and ox-LDL-induced VSMCs. MIAT knockdown suppressed cell proliferation, migration, and invasion in ox-LDL-stimulated VSMCs. MIAT acted as a sponge of miR-490-3p, and miR-490-3p deficiency overturned the inhibition of MIAT knockdown on VSMC proliferation, migration, and invasion. ICAM1 was a direct target of miR-490-3p, and ICAM1 silencing repressed the proliferation, migration, and invasion of ox-LDL-stimulated VSMCs. Moreover, ICAM1 overexpression reversed the impacts of MIAT knockdown on ox-LDL-induced VSMC proliferation, migration, and invasion. MIAT knockdown could depress cell proliferation, migration, and invasion through miR-490-3p/ICAM1 axis in ox-LDL-induced VSMCs.

Long Noncoding RNAs Control the Modulation of Immune Checkpoint Molecules in Cancer.

Long noncoding RNAs (lncRNA) that are associated with immune checkpoints have not been identified, and the mechanism by which such lncRNAs might regulate the expression of immune checkpoints is unknown in human cancer. Immune checkpoint-associated lncRNAs (ICP-lncRNA) were identified and validated via a comprehensive bioinformatic analysis of The Cancer Genome Atlas data. These ICP-lncRNAs were involved in key immune response and immune cell receptor signaling pathways. The expression of ICP-lncRNAs was upregulated and correlated with a poor prognosis in patients with cancer. HLA complex P5 (HCP5) and myocardial infarction associated transcript (MIAT) promoted tumor growth and upregulated the expression of PD-L1/CD274 via a competing endogenous RNA mechanism of sponging miR-150-5p. The combination of MIAT knockdown and PD-L1 antibody administration showed a synergistic inhibitory effect on tumor growth. Finally, the expression of both HCP5 and MIAT was confirmed to be transcriptionally suppressed by CCCTC-binding factor (CTCF), and lipopolysaccharide induced CTCF eviction from the HCP5 and MIAT promoters, attenuating the transcriptionally suppressive activity of CTCF. This study enlarges the functional landscape of known lncRNAs in human cancer and indicates novel insights into their roles in the field of tumor immunity and immunotherapy. These findings may aid in the comprehensive management of human cancer with immunotherapy.

Long non-coding RNA MIAT/miR-148b/PAPPA axis modifies cell proliferation and migration in ox-LDL-induced human aorta vascular smooth muscle cells

AimsAtherosclerosis (AS) performs the important pathogenesis which refers to coronaryheart and vascular diseases. Long non-coding RNAs (lncRNAs) was reported to be related to the AS progression. We aimed to probe the role and potential mechanism of Myocardial Infarction Associated Transcript (MIAT) in AS. Materials and methodsLevels of MIAT, microRNA-148b (miR-148b) and pregnancy-associated plasma protein A (PAPPA) were detected by quantitative Real-time polymerase chain reaction (qRT-PCR) in oxidized low-density lipoprotein (ox-LDL)-induced human aorta vascular smooth muscle cells (HA-VSMCs). Proliferation and migration were examined by Cell counting kit-8 (CCK-8) and wound-healing assays, respectively. Protein levels of Ki-67, proliferating cell nuclear antigen (PCNA), matrix metalloproteinase (MMP)-2, MMP-9 and PAPPA were examined by western blot assay. Ki-67 and PCNA level was detected by flow cytometry. The interaction among MIAT, miR-148b and PAPPA was confirmed via dual-luciferase reporter and RNA immunoprecipitation (RIP). The biology role of MIAT was detected by an AS model in vivo. Key findingsThe levels of MIAT and PAPPA were augmented, whereas mature miR-148b level was repressed in ox-LDL-induced AS model. The inhibitory effects of knockdown of MIAT on proliferation and migration were relieved by miR-148b inhibitor. Additionally, miR-148b regulated proliferation and migration by targeting PAPPA. Mechanically, MIAT functioned as sponge of miR-148b to impact PAPPA expression. MIAT knockdown protected AS mice against lipid metabolic disorders in vivo. SignificanceProliferation and migration were modified by MIAT/miR-148b/PAPPA axis in ox-LDL induced AS cell model, supplying a novel insight into the underlying application of MIAT in the clinical treatment of AS.

Long non‑coding RNA MIAT knockdown potentiates the therapeutic effect of transcatheter arterial embolization in liver cancer by regulating the miR‑203a/HIF‑1α axis.

Transcatheter arterial embolization (TAE) and transcatheter arterial chemoembolization (TACE) are often used for palliative treatment of liver cancer. TAE and TACE can induce severe hypoxia. The present study investigated the effect of the myocardial infarction associated transcript (MIAT)/microRNA (miR)‑203a/hypoxia‑inducible factor1‑α (HIF‑1α) axis on the therapeutic activity of TAE for liver cancer using hypoxia‑treated liver cancer cells and rat orthotopic liver tumors. MIAT, miR‑203a and HIF‑1α mRNA levels were assessed by reverse transcription‑quantitative PCR assay. The protein expression of HIF‑1α, Ki‑67 and vascular endothelial growth factor was determined by western blot assay. The proliferative, migratory and invasive potential of cells was assessed by CCK‑8, Transwell migration and invasion assays, respectively. The association between MIAT, miR‑203a and HIF‑1α was investigated through bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation and RNA pull‑down assay. Invivo experiments were performed to explore the effect of TAE alone or in combination with MIAT knockdown on the growth of rat liver tumors. The results revealed that MIAT and HIF‑1α were highly expressed, and miR‑203a was lowly expressed in liver tumors of patients with liver cancer after TACE treatment and hypoxia‑stimulated liver cancer cells. MIAT sequestered miR‑203a from its target HIF‑1α. MIAT knockdown, miR‑203a overexpression or HIF‑1α loss inhibited proliferation, migration and invasion in hypoxia‑treated liver cancer cells. MIAT knockdown enhanced TAE‑mediated antitumor effects by upregulating miR‑203a and downregulating HIF‑1α in rat liver tumors. In conclusion, MIAT knockdown potentiated the therapeutic effect of TAE in liver cancer by regulating the miR‑203a/HIF‑1α axis invitro and invivo, thus expanding our understanding on the function and molecular basis of MIAT in TAE treatment for liver cancer.

LncRNA MIAT increases cell viability, migration, EMT and ECM production in age-related cataracts by regulating the miR-181a/CTGF/ERK signaling pathway.

Age-related cataract (ARC) is a common cause of blindness in elderly individuals. Long non-coding RNA (lncRNA) myocardial infarction associated transcript (MIAT) has been reported to participate in various biological processes in a number of diseases; however, the biological mechanism underlying MIAT during ARC is not completely understood. The expression levels of MIAT, microRNA (miR)-181a and connective tissue growth factor (CTGF) were measured by reverse transcription-quantitative PCR. The protein expression levels of CTGF, α-smooth muscle actin, fibronectin, collagen type I, ERK, phosphorylated (p)-ERK, mitogen-activated protein kinase (MEK), and p-MEK were detected by western blotting. Cell viability and migration were assessed using MTT and Transwell assays, respectively. Moreover, a dual-luciferase reporter assay was performed to investigate the interaction between miR-181a and MIAT or CTGF. MIAT and CTGF were upregulated, while miR-181a was significantly downregulated in ARC tissues compared with normal tissues. MIAT or CTGF knockdown decreased cell viability, migration, epithelial-mesenchymal transition and extracellular matrix production in TGF-β2-treated SRA01/04 cells. It was hypothesized that miR-181a may be sponged by MIAT and may target CTGF. Furthermore, the miR-181a inhibitor reversed the inhibitory effect of MIAT knockdown on the progression of TGF-β2-treated SRA01/04 cells. Moreover, CTGF knockdown also reversed MIAT overexpression-mediated progression of TGF-β2-treated SRA01/04 cells. In addition, MIAT and CTGF regulated the activity of the ERK signaling pathway. The results suggested that MIAT may regulate the progression of ARC via the miR-181a/CTGF/ERK signaling pathway, which may serve as a novel therapeutic target for ARC.

LncRNA MIAT Regulates Cell Growth, Migration, and Invasion Through Sponging miR-150-5p in Ovarian Cancer.

Background: MIAT (myocardial infarction-associated transcript) regulates cell proliferation, apoptosis, and metastasis in several cancers. In this study, the authors aimed to explore the role of MIAT in ovarian cancer. Materials and Methods: The expression of MIAT in ovarian cancer subtypes, normal human ovarian surface epithelial and ovarian cancer cell lines was measured by qualitative real-time polymerase chain reaction (qRT-PCR). OVCAR3 and SKOV3 cells were transfected with MIAT overexpression plasmid or siMIAT. The cell growth ability was then evaluated by CCK-8 and colony formation assays. The cell migration and invasion rate were separately measured by wound-healing and transwell assays. The levels of epithelial-mesenchymal transition (EMT)-associated markers were evaluated by Western blotting. MIAT sponging miR-150-5p was predicted by starBase and confirmed by dual-luciferase reporter assays. The expression of miR-150-5p in OVCAR3 and SKOV3 cells with MIAT overexpression or knockdown, and in ovarian cancer subtypes was also measured by qRT-PCR. Further analyses confirmed the role of MIAT sponging miR-150-5p in ovarian cancer cells. Results: MIAT was highly expressed in mesenchymal subtype ovarian cancer tissues and ovarian cancer cells. In OVCAR3 and SKOV3 cells, overexpression of MIAT promoted, and knockdown of MIAT suppressed the cell growth, migration, invasion, and EMT. miR-150-5p was sponged and regulated by MIAT. miR-150-5p was downregulated in mesenchymal subtype ovarian cancer. Suppression of cell migration, invasion, and EMT caused by miR-150-5p overexpression was rescued by MIAT overexpression. Conclusions: MIAT acts as an oncogene in ovarian cancer cells through sponging miR-150-5p. MIAT or miR-150-5p expression might be a potential prognostic biomarker for ovarian cancer patients. MIAT and miR-150-5p are potential therapeutic targets in treatment of ovarian cancer.

Long non-coding RNA myocardial infarction associated transcript promotes the proliferation of cholangiocarcinoma cells by targeting miR-551b-3p/CCND1 axis.

Accumulating reports have demonstrated that long non-coding RNAs (lncRNAs) play critical roles in the occurrence and metastasis of cholangiocarcinoma (CCA). LncRNA myocardial infarction associated transcript (MIAT) has been widely reported in hepatocellular carcinoma, pancreatic cancer and colorectal cancer, but the relationship between MIAT and CCA progression has not yet been investigated. In the present study, we found that the expression of MIAT in CCA tissues was prominently higher than that in normal bile duct tissues. Moreover, TCGA-CHOL data in the GEPIA platform further revealed the upregulated expression of MIAT in CCA tissues. Additionally, quantitative real-time PCR results showed that MIAT expression was increased in CCA cell lines compared to the human intrahepatic biliary epithelial cell line. Functionally, MIAT knockdown significantly inhibited cell proliferation and induced G0/G1 phase arrest as well as apoptosis in HuCCT-1 and QBC939 cells. Conversely, ectopic expression of MIAT obviously facilitated the proliferation, cell cycle progression and apoptosis resistance of RBE cells. Mechanistically, MIAT directly interacted with miR-551b-3p and inversely modulated miR-551-3p level in CCA cells. Furthermore, MIAT knockdown reduced the expression of cyclin D1 (CCND1), which was rescued by miR-551b-3p silencing in HuCCT-1 cells. Importantly, CCND1 restoration partially reversed MIAT knockdown-induced proliferation inhibition, G0/G1 phase arrest and apoptosis in HuCCT-1 cells. In conclusion, MIAT was frequently overexpressed in CCA. MIAT contributed to the growth of CCA cells by targeting miR-551b-3p/CCND1 axis.