Effects Of MALAT1 Research Articles

Suppression of MALAT1 promotes human synovial mesenchymal stem cells enhance chondrogenic differentiation and prevent osteoarthritis of the knee in a rat model via regulating miR-212-5p/MyD88 axis.

Osteoarthritis (OA) is one of the most common diseases of the skeleton. Long non-coding RNAs (lncRNAs) are emerging as key players in OA pathogenesis. This work sets out to determine the function of lncRNA MALAT1 in OA and the mechanisms by which it does so. Mesenchymal stem cells isolated from the human synovial membrane are called hSMSCs. The hSMSCs' surface markers were studied using flow cytometry. To determine whether or not hSMSC might differentiate, researchers used a number of different culture settings and labeling techniques. The expression levels of associated genes and proteins were determined using quantitative real-time polymerase chain reaction (RT-qPCR), western blotting (WB), and immunostaining. A dual luciferase reporter experiment and RNA immunoprecipitation (RIP) test demonstrated the direct association between miR-212-5p and MALAT1 or MyD88. MALAT1 was downregulated during the chondrogenic differentiation of hSMSCs, and underexpression of MALAT1 promotes chondrogenesis in hSMSCs. Using dual luciferase reporter and RIP assays facilitated the identification of MALAT1 as a competitive endogenous RNA (ceRNA) that sequesters miR-212-5p. Additionally, the expression of MYD88 was regulated by MALAT1 through direct binding with miR-212-5p. Significantly, the effects of MALAT1 on the chondrogenic differentiation of hSMSCs were counteracted by miR-212-5p/MYD88. Furthermore, our in vivo investigation revealed that the inhibition of MALAT1 mitigated osteoarthritis progression in rat models. In conclusion, the promotion of chondrogenic differentiation in hSMSCs and the protective effect on cartilage tissue in OA can be achieved by suppressing MALAT1, which regulates the miR-212-5p/MyD88 axis.

MALAT1 participates in the role of platelet-rich plasma exosomes in promoting wound healing of diabetic foot ulcer

Exosomes isolated from platelet-rich plasma (PRP-exos) have been recently deemed as an optimized therapeutic strategy in diabetic foot ulcer (DFU) treatment. Herein, we aimed to explore whether MALAT1 participates in DFU wound healing by PRP-exos treatment and the related preliminary mechanism. Fibroblasts were isolated from healthy donors and DFU patients, and the expression of MALAT1, miR-374a-3p and DNMT3A were detected by RT-PCR. The effect of MALAT1 and miR-374a-3p on DFU fibroblast function was verified by gain/loss of function experiment. The targeted binding of MALAT and miRNA was verified by double luciferase reporter gene assay. PRP-exos were isolated from normal human blood and characterized, and then co-cultured with DFU fibroblasts. The MALAT1 expression was donwregulated while the miR-374a-5p expression was upregulated in DFU fibroblasts. Double luciferase reporter gene assay demonstrated the targeted binding of MALAT and miR-374a-5p. Overexpression of MALAT1 or knockdown of miR-374a-5p could increase viability and inhibit apoptosis and pyroptosis of DFU fibroblast. And overexpression of miR-374a-5p reversed the effect of PRR-exos or MALAT1 overexpression on cell viability, apoptosis and pyroptosis. Collectively, MALAT1 mediated signal axis participates in the role of PRP-exos in promoting DFU wound healing, which may help identify optimal targets and effective therapies for DFU treatment.

LncRNA MALAT1 from human adipose-derived stem cell exosomesaccelerates wound healing via miR-378a/FGF2 axis.

Aim: The effects of MALAT1from human adipose-derived stem cell(ADSC) exosomes in skin wound healingwere investigated. Material & methods: The viability, apoptosisand migration ability of human skin fibroblasts (HSFs) were evaluated by Cell Counting Kit-8 assay, flow cytometryand scratch assay, respectively. A mouse model was established to evaluate the role of exosomal MALAT1 in skin wound healing in vivo. Results: Human ADSC exosomes promoted the proliferation and migration of HSFs and increased MALAT1 expression. MALAT1 silencing in human ADSCs inhibited HSF viability and migration, promoted HSF apoptosisand inhibited angiogenesis by upregulating miR-378a. Overexpression of miR-378a inhibited the migration and proliferation of HSFs by downregulating FGF2expression. ADSC exosomes promoted skin wound healing by mediating MALAT1 in vivo. Conclusion: Exosomal MALAT1 accelerated skin wound healing by regulating the miR-378a/FGF2 axis, suggesting that MALAT1 might be used as a potential target for cutaneous wound treatment.

Knockdown of Malat1 alleviates high-glucose-induced angiogenesis through regulating miR-205-5p/VEGF-A axis

Diabetic retinopathy (DR), characterized by intraretinal vessel formation, is a major complication in diabetes. Neovascularization is an important characteristic of DR, but its formation mechanism remains unclear. In this research, Malat1, miR-205-5p, and VEGF-A levels in high glucose (HG) treat-human retinal microvascular endothelial cells (hRMECs) was detected with qRT-PCR. CCK-8 assay, transwell assay, and tube formation assay was applied to access hRMEC viability, migration, and angiogenesis. Expression level of endothelial-mesenchymal transition (EndMT) markers (VE-cadherin, FSP1, and α-SMA) was detected by western blotting assay. Interaction among Malat1, miR-205-5p, and VEGF-A was confirmed by dual-luciferase reporter assay. Furthermore, in vivo DR mouse model was induced, and the effect of Malat1 on DR and EndMT markers was confirmed through hematoxylin-eosin (HE) staining and western blotting. As a result, Malat1 and VEGF-A was upregulated while miR-205-5p was suppressed under HG conditions. Malat1 could sponge miR-205-5p to regulate VEGF-A expression. Malat1 knockdown inhibited hRMEC proliferation, migration, and tube formation by targeting miR-205-5p under HG conditions. Furthermore, inhibition of Malat1 prevented the HG-induced EndMT process. In summary, Malat1 knockdown diminished hRMEC dysfunctions by regulating miR-205-5p/VEGF-A, providing a useful insight for exploring new therapeutic target for DR.

MALAT1/miR-320a in bone marrow mesenchymal stem cells function may shed light on mechanisms underlying osteoporosis.

Growing evidence supports the involvement of long noncoding RNAs (lncRNAs) in bone metabolism and diseases. This study aims to investigate the involvement of the lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the pathological process of osteoporosis and the effects of MALAT1 on regulation of BMSC differentiation through competitive endogenous RNA (ceRNA) mechanisms. The expression of MALAT1 and miR-320a was determined using RT-PCR in bone tissue derived from female SD (Sprague Dawley) rats with osteoporosis. Immunohistochemical (IHC) staining was used to evaluate the expression of neuropilin-1 (NRP-1) and β-catenin. Bone marrow mesenchymal stem cells (BMSCs) were divided into 4 groups: control, NC (negative control), MALAT1 siRNA, and miR-320a mimics. Forty-eight hours later, the effect of MALAT1 on the miR-320a expression, proliferation and osteogenic differentiation of BMSCs was investigated. Two weeks later, the cell activity, alkaline phosphatase (ALP) activity, and mRNA expression of Osterix and Runx2 were evaluated. Three weeks later, alizarin red staining of calcified nodules and Western blot analysis of the expression of β-catenin, NRP-1, osteocalcin (OCN), and osteopontin (OPN) were performed. Downregulated MALAT1or upregulated miR-320a expression inhibited the activity and osteogenic differentiation of BMSCs, resulting in low ALP activity and NRP-1 expression, fewer calcified nodules, decreased mRNA levels of Osterix and Runx2, and inhibited expression of NRP-1, OCN, and OPN. MALAT1 silencing did not decrease the protein level of β-catenin in the cytoplasm but suppressed that in the nucleus. Downregulated MALAT1 and upregulated miR-320a expression play an important role in the pathological process of osteoporosis, via inhibition of the osteogenic differentiation of BMSCs.

MALAT1 knockdown promoted cell viability and migration of LPS-treated MG-63 cells via sponging miR-212.

Most fractures could heal after treatment, around 5-10 % of patients still develop delayed union and nonunion. Evidence has increasingly shown that abnormal expression of long noncoding RNAs is closely related to the occurrence and development of various diseases including fracture healing. However, evidence regarding the effect of MALAT1 on fracture healing remains limited. In this study, we attempt to explore the role of MALAT1 during the process of femoral neck fracture healing and elucidate the underlying mechanism of this disease. We first detect the expression of lncRNAs in serums from 3 pairs of patients with delayed femoral neck fracture healing and healthy volunteers using lncRNA microarray. And the expression of long noncoding RNA MALAT1 in serums and LPS-treated MG-63 cells was measured using qRT-PCR. CCK-8 assay, cell migration and qRT-PCR were applied to the role of MALAT1 knockdown in LPS-treated MG-63 cells. ELISA was used for the measurement of inflammatory cytokines in serums of patients and healthy volunteers. The bioinformatics analysis and the rescue experiment were devoted to the underlying mechanism. MALAT1 expression was up-regulated in serum of patients with delayed union of femoral neck fracture. MALAT1 knockdown promoted cell viability and migration, reduced inflammation in LPS-treated MG-63 cells. The bioinformatics analysis showed MALAT1 acts as a molecular sponge for miR-212. And SOX6 was a target of miR-212. Besides, MALAT1 knockdown suppressed SOX6 expression via targeting miR-212 in LPS-treated MG-63 cells. These data suggest MALAT1 knockdown promoted the biological behavior of LPS-treated MG-63 cells via sponging miR-212, which may provide a new therapeutic avenue for delayed union of femoral neck fracture.

Down-regulation of MALAT1 aggravates polycystic ovary syndrome by regulating MiR-302d-3p-mediated leukemia inhibitory factor activity

AimsAccumulating evidence have shown the important roles of long noncoding RNA (lncRNA) in controlling different diseases. In the present study, we tried to explore the role which lncRNA MALAT1 plays in polycystic ovary syndrome (PCOS) with the involvement of microRNA-302d-3p (miR-302d-3p) and leukemia inhibitory factor (LIF). MethodsA PCOS rat model was established and characterized, followed by treatment with si-MALAT1, oe-MALAT1, miR-302d-3p mimic, or miR-302d-3p inhibitor constructs. Serum hormonal levels were detected to evaluate endocrine conditions. The effect of MALAT1 and miR-302d-3p on activities of ovarian granulosa cells was assessed, as well as the involvement of LIF. ResultsMALAT1 expression was shown to be downregulated in ovarian tissue of PCOS rats. Overexpression of MALAT1 in vitro promoted proliferation and inhibited apoptosis of ovarian granulosa cells. Overexpression of MALAT1 in vivo reduced the ovarian tissue injury and endocrine disorders accompanied with decreased level of FSH and elevated serum levels of E2, T, and LH in the PCOS rat. Overexpression of MALAT1 also promoted the expression of LIF, which could be reversed by overexpression of miR-302d-3p, indicating that MALAT1 up-regulated the expression of LIF via miR-302d-3p. Furthermore, overexpression of MALAT1 reduced endocrine disorders and ovarian tissue damage via the miR-302d-3p/LIF axis. ConclusionOur study highlighted that MALAT1 plays a protective role in reducing ovarian tissue damage and endocrine disorder in PCOS by regulating the miR-302d-3p/LIF axis.

LncRNA MALAT1 affects the migration and invasion of trophoblast cells by regulating FOS expression in early-onset preeclampsia.

Preeclampsia (PE), particularly early-onset PE (ePE), causes maternal and fetal complications and remains a major health problem in modern society. Aberrant uterine spiral artery remodeling leads to ePE through poor placentation. In this study, we investigated the role of the long non-coding RNA (lncRNA) MALAT1 in ePE pathogenesis. Total RNA was extracted from 40 paired placental ePE tissues and control groups. RNA levels were quantified by qRT-PCR and protein expression was determined by western blotand immunohistochemistry (IHC) analysis. The effects of MALAT1 on trophoblast migration and invasion were evaluated in HTR-8/SVneo and JAR cells. FOS was identified as a downstream functional gene of MALAT1 by RNA-seq. RNA binding protein immunoprecipitations (RIPs) were performed to reveal the cellular targets of MALAT1. MALAT1 was poorly expressed in ePE placentas and its silencing (-/-) inhibited trophoblast invasion and migration. MALAT1 -/- also decreased N-cadherin and vimentin expression, but increased E-cadherin expression. RNA-seq analysis and subsequent RIP assays showed that MALAT1 improved FOS through Hu-antigen R (HuR) binding. FOS overexpression similarly enhanced trophoblast migration and invasion. IHC staining showed that E-cadherin was upregulated in placenta tissue from ePE groups, whilst FOS, N-cadherin, and vimentin were downregulated. MALAT1 promotes trophoblast migration and invasion through FOS-induced epithelial mesenchymal transition (EMT). This highlights new roles for MALAT1 in the impairment of spiral artery remodeling in ePE pathogenesis.

RETRACTED: Aberrant expression of lncRNA MALAT1 modulates radioresistance in colorectal cancer in vitro via miR-101-3p sponging

Colorectal cancer (CRC) is one of deadly malignancies that affects humans globally. Herein, the effects of MALAT1 on CRC cellular functions were investigated. RT-qPCR measured expression of MALAT1 in human cell lines for colorectal Cancer. Radiation-resistance CRC cells (CRC-IR) were generated by increasing treatments of irradiation. Cell transfection upregulated or silenced genes in CRC-IR cells so as to study the correlation between MALAT1/miR-101-3p expression and cellular resistance to irradiation through evaluation of CCK-8, FCM apoptosis, Transwell migration and invasion and western blot assays for cell viability,apoptosis, migration and invasion and EMT. MALAT1 was upregulated in radio-resistance cell lines compared to normal CRC cells and upregulation promoted cell viability. In addition, decreased MALAT1 inhibited cell proliferation and metastasis and promoted apoptosis of CRC-IR cells. The luciferase assays confirmed that MALAT1 targeted and regulated miR-101-3p expression in radio-resistance cells. MiR-101-3p counteracted the effect exerted by MALAT1 in CRC-IR cells, indicating that MALAT1 added to the radio-resistance in vitro while miR-101-3p mimics could decrease the resistance to irradiation in CRC. In this study we have demonstrated that MALAT1 could regulate the radio-resistance in colorectal cancer via sponging miR-101-3p. Eventually, these outcomes unearthed a novel axis lncRNA MALAT1/miR-101-3p,which might be a prospective treatment to regulate radio-therapy in the near future.

LncRNA MALAT1 exhibits positive effects on nucleus pulposus cell biology in vivo and in vitro by sponging miR-503

BackgroundIntervertebral disc degeneration (IDD) is characterized by the loss of nucleus pulposus cells (NPCs) and phenotypic abnormalities. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) are involved in the pathogenesis of IDD. In this study, we aimed to investigate the functional effects of lncRNA MALAT1 on NPCs in IDD and the possible mechanism governing these effects.ResultsWe validated the decreased expression of MALAT1 in the IDD tissues, which was associated with decreased Collagen II and Aggrecan expression. In vitro, overexpressed MALAT1 could attenuate the effect of IL-1β on NPC proliferation, apoptosis, and Aggrecan degradation. In vivo, MALAT1 overexpression attenuated the severity of disc degeneration in IDD model rats. Our molecular study further demonstrated that MALAT1 could sponge miR-503, modulate the expression of miR-503, and activate downstream MAPK signaling pathways. The effects of MALAT1 on NPCs were partially reversed/aggregated by miR-503 mimics/inhibitor treatment.ConclusionOur data suggested that the MALAT1-miR-503-MAPK pathway plays a critical role in NPCs, which may be a potential strategy for alleviating IDD.

Correlation Between Single Nucleotide Polymorphisms of the rs664589 Locus in the Long-Chain Noncoding RNA Lung Adenocarcinoma Metastasis-Associated Gene 1, Hypertension, and Its Mechanism.

Objective: Hypertension is a disease caused by both genetic and environmental factors. In the present study, we analyzed the association of the lung cancer adenocarcinoma metastasis-associated gene 1 (MALAT1) gene rs664589 locus single nucleotide polymorphism (SNP) with the risk of essential hypertension and explored its possible mechanisms. Materials and Methods: We analyzed the genotype of the MALAT1 gene rs664589 locus in 260 hypertensive patients and 260 healthy controls. The levels of plasma long-chain noncoding RNA (lncRNA) MALAT1, hsa-miR-539-3p, and hsa-miR-485-3p were determined by reverse transcription real-time quantitative PCR (qRT-PCR). The effects of MALAT1 on the expression levels of hsa-miR-539-3p, hsa-miR-485-3p, and bone morphogenetic protein receptor type 2 (BMPR2) were detected by transfection of human umbilical vein endothelial cells. Results: The risk of hypertension in subjects carrying the G allele of the MALAT1 gene rs664589 locus was 1.33 times higher than the C allele carriers (95% confidence interval [CI]: 1.15-1.51, p < 0.001). This MALAT1 gene rs664589 locus SNP was significantly associated with the risk of hypertension only in men, subjects with obesity, a history of smoking, and a history of drinking (p < 0.05). lncRNA MALAT1 was downregulated in the plasma of hypertensive patients. In addition, the level of plasma lncRNA MALAT1 was significantly lower in the G allele carriers of the MALAT1 gene than in the C allele carriers (p < 0.001). The lncRNA MALAT1 inhibited the expression of hsa-miR-539-3p and hsa-miR-485-3p and promoted the expression of the BMPR2 protein. Conclusion: The G allele of MALAT1 gene rs664589 locus SNP is associated with an increased risk of hypertension. In subjects carrying the G allele, the expression of lncRNA MALAT1 in plasma is significantly decreased, resulting in an abnormally high expression of hsa-miR-539-3p and hsa-miR-485-3p, and inhibition of BMPR2 expression, which might be associated with hypertension; however, further studies in animal models are needed to confirm this hypothesis.

The knockdown of MALAT1 inhibits the proliferation, invasion and migration of hemangioma endothelial cells by regulating MiR-206 / VEGFA axis

AimLncRNA MALAT1 is involved in regulation of angiogenesis, however, its expression and mechanism in infantile hemangioma (IH) are less reported. The study aimed to investigate MALAT1 in IH and to reveal the potential mechanism of MALAT1 acting on IH. MethodsIsolated form IH tissue, human CD31+ hemangioma endothelial cells (HemECs) were cultured and sorted by magnetic-activated cell sorting (MACS). Quantitative real-time (qRT)-PCR was performed to detect the expressions of MALAT1, miR-206 and VEGFA. The correlations among MALAT1, miR-206 and VEGFA were confirmed by bioinformatics analysis and dual-luciferase reporter assay. The effects of MALAT1, miR-206 and VEGFA on cell proliferation were detected by cell counting kit-8 (CCK-8) and cell colony formation assay. Flow cytometry, wound scratch, Transwell and Tube formation assay were performed to determine cell apoptosis, migration, invasion and vasoformation, respectively. Apoptosis-related proteins were determined by Western blot. ResultsThe results showed that MALAT1 and VEGFA were high-expressed and miR-206 was low-expressed in IH tissues. SiMALAT1 negatively affected the cell proliferation, migration, invasion and vasoformation of HemECs and promoted apoptosis of HemECs. Moreover, Bcl-2 expression was significantly inhibited and the expressions of Bax and c cleaved-3 were greatly promoted. MALAT1 directly targeted and inhibited the expression of miR-206, and VEGFA was predicted to be the target gene for miR-206. SiMALAT1 suppressed the cell proliferation, migration, invasion and vasoformation of HemECs through modulating miR-206/VEGFA axis. ConclusionKnock-down of MALAT1 inhibits the growth of HemECs through regulating miR-206/VEGFA axis, indicating that MALAT1 is a potential therapeutic mechanism for the treatment of IH.

MALAT1 accelerates the development and progression of renal cell carcinoma by decreasing the expression of miR-203 and promoting the expression of BIRC5.

ObjectiveWe aimed to investigate the roles of the lncRNA MALAT1 in renal cell carcinoma (RCC) progression.MethodsqRT‐PCR was used for the assessment of BIRC5, miRNA‐203 and MALAT1 expression. Furthermore, the targeted relationships between miR‐203 and BIRC5, as well as MALAT1 and miR‐203, were predicted by the miRanda/starBase database and verified by dual‐luciferase reporter gene assay. The effects of MALAT1, miRNA‐203 and BIRC5 on cell proliferation, cell cycle, cell apoptosis, cell invasion and cell migration were studied by using CCK‐8, flow cytometry, transwell and wound healing assays, respectively. In addition, the effects of MALAT1 on RCC tumorigenesis were evaluated in vivo by nude mouse tumorigenesis.ResultsThe expression levels of BIRC5 and MALAT1 were higher in RCC tissues and cell lines than in adjacent normal tissues and a normal renal cortex proximal tubule epithelial cell line. In contrast, the expression of miRNA‐203 in RCC tissues and cell lines was higher than that in adjacent normal tissues and a normal renal cortex proximal tubule epithelial cell line. BIRC5 and MALAT1 promoted cell proliferation yet decreased the percentage of RCC cells at G0/G1 phase.ConclusionsOur study demonstrated that MALAT1 functions as a miR‐203 decoy to increase BIRC5 expression in RCC.

Long noncoding RNA MALAT1 mediates stem cell-like properties in human colorectal cancer cells by regulating miR-20b-5p/Oct4 axis.

Cancer stem cells (CSCs) are crucial components of the tumor microenvironment that take part in tumor initiation, progression, recurrence, metastasis, and resistance to chemotherapy. This study explores the mechanisms through which CSCs maintain their stemness, especially in tumors of colorectal cancer (CRC), which thus far remain uncertain. Our findings indicated that the expression of miR-20b-5p is negatively correlated with that of metastasis-associated lung adenocarcinoma transcript-1 (MALAT1, r = -0.928, p = 0.023) and Oct4 (r = -0.894, p = 0.041) in CRC cells. We hypothesized that there may be some targeted regulatory relationships among MALAT1, miR-20b-5p, and Oct4. We proceeded to show that both si-MALAT1 and miR-20b-5p-mimic attenuated microsphere formation and self-renewal capacity, decreased the proportion of CSCs, and downregulated the expression of proteins associated with tumor cell stemness maintenance (Oct4, Nanog, sex-determining region Y-box 2, and Notch1) and cellular metabolism (glucose transporter 1, lactate dehydrogenase B, hexokinase 2, and pyruvate kinase isozyme M2) in HCT-116 cells in vitro. In addition, a xenograft model based on Balb/c mice demonstrated that the administration of either si-MALAT1 or miR-20b-5p-mimic suppressed the tumorigenicity of HCT-116 cells in vivo. The underlying mechanisms may involve the targeting of the tumor cell stemness maintenance-related factor Oct4 by miR-20b-5p. For the first time, we present the possible underlying effects of MALAT1 in influencing the stem cell-like properties of CRC cells. We propose that microRNAs and longnoncoding RNAs have vital functions in mediating tumor stemness, which remain to be fully elucidated.

The effects of lncRNA MALAT1 on proliferation, invasion and migration in colorectal cancer through regulating SOX9

BackgroundFor the study, we determine the potential biomarkers and uncover the regulatory mechanisms of lncRNA MALAT1 / miR-145 / SOX9 axis on the abilities of cell growth and cell metastasis of colorectal cancer.MethodsPreviously published dataset GSE18105 from GEO database was used for microarray analysis to identify differential-expressed lncRNAs and mRNAs. The miRNA which had targeted relationships with both lncRNA and mRNA was predicted using miRCode and Targetscan. The association between lncRNA and miRNA, miRNA and mRNA was verified using dual-luciferase reporter assay.Expression levels of lncRNA MALAT1, miR-145 and SOX9 were examined by quantitative RT-PCR analysis. The cell viability of two cancer cell lines was compared by CCK-8 assay. Colony formation was hired to detected cell proliferation. The cell cycle distribution and apoptotic cell rate were conducted by flow cytometry assay. Wound healing as well as transwell assay were compare the cell migration and cell invasion respectively among groups. The effect of MALAT1 on colorectal cancer in vivo was constructed by xenograft model.ResultsSignificantly dysregulated lncRNAs and mRNAs were identified by microarray analysis. By experimental verification, MALAT1 and SOX9 were expressed in a high percentage of colorectal cancer tumors and cells, while miR-145 was in a low expression. We also identified miR-145 as a target of MALAT1 and SOX9. MALAT1 played a role in regulating cancer process by functioning as a competing endogenous RNA. Silencing MALAT1 could effectively decrease the expression level of SOX9, thus suppress cell viability and metastasis. Down-regulated MALAT1 could induce resistance of G1 phase in cell cycle, and facilitation of colorectal cancer cell apoptosis. Nude mice injected with cells transfected with si-MALAT1 had smaller tumor on size and weight.ConclusionsThe regulatory function of lncRNA MALAT1 / miR-145 / SOX9 axis was revealed in colorectal cancer based on bioinformatics analysis. LncRNA MALAT1 could facilitate colorectal cancer cell proliferation, invasion and migration by down-regulating miR-145 and up-regulating SOX9. LncRNA MALAT1 could suppress cell cycle and apoptosis through MALAT1 / miR-145 / SOX9 axis.

Long chain non-coding RNA MALAT-1 gene knockdown inhibits growth and migration and promotes apoptosis of human laryngeal squamous cell carcinoma Hep-2 cells in vitro

To investigate the effect of knocking down long chain non-coding RNA MALAT-1 gene on the biologicalbehaviors of human laryngeal squamous cell carcinoma Hep-2 cells. With immortalized nasopharyngeal epithelial(NPE) cell line NP-69 as the reference, MALAT1 expression in FaDu, Hep-2 and nasopharyngeal carcinoma CNE-2Z cells weredetected using real-time PCR. Hep-2 cells were transfected with shmalat1 lentivirus and the expression of MALAT1 wasdetected. MTT assay, flow cytometry, Transwell assay and M Atrigel invasiveness test were used to evaluate the effect ofMALAT-1 knockdown on the proliferation, cell cycle, cell apoptosis, migration, and invasiveness of Hep-2 cells. Compared with NP-69 cells, Hep-2 cells, FaDu cells, and CNE-2Z cells all showed significantly increased MALAT-1expression. In Hep-2 cells, knockdown of MALAT-1 significantly inhibited the cell proliferation, increased the cell percentagein S phase (P < 0.01), decreased the cell percentage in G2/M phase (P < 0.01), and attenuated the migration and invasiveness of thecells. MALAT-1 is over-expressed in laryngeal squamous cell carcinoma, and knocking down MALAT-1 gene cansignificantly suppress the proliferation, invasion and migration and promotes apoptosis of the cancer cells.

Effects of MALAT1 on proliferation and apo- ptosis of human non-small cell lung cancer A549 cells in vitro and tumor xenograft growth in vivo by modulating autophagy.

To explore the ability of MALAT1 to influence non-small cell lung cancer (NSCLC) A549 cells in vitro and tumor xenograft growth in vivo by modulating autophagy. LncRNA MALAT-1 in normal HBE cells and human NSCLC cells was measured. A549 cells were treated with si-MALAT-1, negative control and si-MALAT-1 + rapamycin. The mRNA levels of MALAT-1, P62 and LC3 was determined by the qRT-PCR and the protein levels of autophagy-related proteins by the western blotting. The CCK8 assay was performed for cell proliferation, the scratch test for cell migration, the Transwell assay for cell invasion, and the flow cytometry for cell cycle and apoptosis. Tumor xenograft in nude mice is performed to test tumorigenesis of the transfected A549 cells. The expression level of MALAT-1 in A549, SPC-A-1 and NCI-H460 cells was increased compared to HBE cells. And A549 with a high expression level of MALAT-1 were selected for cell transfection. si-MALAT-1 decreased cell proliferation, migration, invasion, and LC3-II/LC3-I ratio, reduced cell cycle progression, and increased cell apoptosis and P62 protein expression. No significant difference was found between A549 cells and A549 cells transfected with si-MALAT-1 + RAPA, A549 cells transfected with NC and A549 cells transfected with si-MALAT-1 + RAPA. Nude mice injected with A549 cells transfected with si-MALAT-1 had smallest tumor on size and weight among other nude mice. Downregulation of MALAT1 may promote apoptosis and suppress proliferation, migration and invasion of human NSCLC A549 cells by inhibiting autophagy, thereby suppressing the development of NSCLC.

The investigation of functions of metastasis associated lung adenocarcinoma transcript 1 in migration/invasion of colorectal cancer cells

Objective To investigate the expression and clinical value of long non-coding RNA MALAT1 in colorectal cancer tissues. We also set to interpret the roles and the possible mechanismsof MALAT1 in cell migration/invasion of colorectal cancer cells. Methods Real-time quantitative polymerase chain reaction (Real-time PCR) was applied to examine the expression of MALAT1 in paired colorectal cancer tissues and normal tissues. MALAT1 was knocked down by small interfering RNA (siRNA) in SW620 cells. Wound healing and transwell assay were performed to evaluate the effects of MALAT1 on the migration and invasion abilities respectively. Western blotting was finally used to detect the expression of epithelial-mesenchymal transition (EMT) markers. Results MALAT1 was significantly increased in colorectal cancer tissues. MALAT1 was up-regulated in colorectal cancer tissue compare 46.7% (14/30) compared with normal tissue with statistical difference (P<0.05); Transient inhibition of MALAT1 in SW620 cells resulted in decreased cell migration/invasion. The expression of EMT markers were down-regulated after MALAT1 was knocked down. Conclusion Up-regulation of MALAT1 in colorectal promotes cell migration/invasion, which might be mediated by inducing EMT. Key words: Metastasis-associated lung adenocarcinoma transcript 1; Colorectal cancer; Neoplasm metastasis; Epithelial-mesenchymal transition