Ginsenoside Rh7 Suppresses Proliferation, Migration and Invasion of NSCLC Cells Through Targeting ILF3-AS1 Mediated miR-212/SMAD1 Axis.
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ABSTRACT:
SUBMITTER: Chen X
PROVIDER: S-EPMC8116958 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Melanoma is the most malignant skin cancer, which account for most of skin-cancer-related deaths. Long noncoding RNA (lncRNA) is a class of noncoding RNAs with crucial roles in many cancers. However, the roles of lncRNAs in melanoma have not been well studied. In the present study, using public available data and clinical tissues samples, we found that lncRNA ILF3-AS1 is up-regulated in melanoma tissues and cell lines, and correlated with poor prognosis of melanoma patients. Functional experiments showed that knockdown of ILF3-AS1 inhibits melanoma cell proliferation, migration, and invasion. Mechanistically, we found that ILF3-AS1 interacts with EZH2, promotes the binding of EZH2 to the miR-200b/a/429 promoter, and represses miR-200b/a/429 expression. The expression of ILF3-AS1 is negatively correlated with that of miR-200b/a/429 in melanoma tissues. Moreover, inhibition of miR-200b/a/429 abrogates the biological roles of ILF3-AS1 knockdown on melanoma cell proliferation, migration, and invasion. In conclusion, these results demonstrate that melanoma-upregulated lncRNA ILF3-AS1 promotes cell proliferation, migration, and invasion via negatively regulating miR-200b/a/429, and imply that ILF3-AS1 may be a potential prognostic biomarker and therapeutic target for melanoma.
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Project description:UnlabelledTwist1 is well known to induce epithelial-mesenchymal transition (EMT) and promote tumor metastasis. MicroRNAs (miRNAs) are involved in the EMT process and are associated with metastasis in hepatocellular carcinoma (HCC). In the present study, microRNA-26b-5p (miR-26b-5p) expression was consistently and significantly downregulated in HepG2-Twist1 HCC cell lines compared with HepG2-vector cell lines using microarrays (the HepG2-Twist1 cell line can stably express Twist1). miR-26b- 5p downregulation was directly mediated by Twist1 through binding to the promoter region of miR-26b-5p in HepG2-Twist1 cells by ChIP-seq technology. Both gain- and loss-of-function studies showed that miR-26b-5p dramatically suppressed EMT and the invasion ability of HCC cells in vitro. Using mouse models, tumors derived from miR- 26b-5p-overexpressed HCC cells exhibited a significant reduction in tumorigenicity compared with the control group. Subsequent investigation revealed that miR-26b-5p directly inhibited SMAD family member 1 (SMAD1) expression. miR-26b-5p repressed BMP4/Smad1 signaling following SMAD1 inhibition. Overexpression of SMAD1 reversed the function of miR-26b-5p. In human HCC tissues and mouse xenograft tumors, miR-26b-5p levels were inversely correlated with SMAD1 expression as well as metastasis.ConclusionmiR-26b-5p suppresses Twist1-induced EMT, invasion, and metastasis of HCC cells by targeting SMAD1 and BMP4/Smad1 signaling. This suggests a promising application for miR-26b-5p in anti-HCC therapy.
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Project description:ObjectiveLong noncoding RNA FGD5 antisense RNA 1 (FGD5-AS1) participates in the regulation of non-small cell lung cancer (NSCLC) progression, but the underlying mechanisms are not fully revealed. This study aimed to determine the regulatory mechanism of FGD5-AS1 on the viability, migration, and invasion of NSCLC cells.MethodsQRT-PCR was performed to measure the expression of FGD5-AS1, microRNA-944 (miR-944), and MACC1 in NSCLC. The correlation between FGD5-AS1 and clinicopathological features of NSCLC patients was analyzed. The viability of NSCLC cells were detected using MTT assay, and the migration and invasion were measured by transwell assay. Additionally, dual-luciferase reporter assay was used to demonstrate the interactions among FGD5-AS1, miR-944, and MACC1. Furthermore, exosomes were isolated from NSCLC cells and identified by transmission electron microscopy (TEM) and western blot. Then, the macrophages treated with exosomes were co-cultured with NSCLC cells to assess the effect of exosomes containing lower FGD5-AS1 level on NSCLC.ResultsThe expression of FGD5-AS1 and MACC1 was increased in NSCLC, but miR-944 expression was decreased. FGD5-AS1 expression had significantly correlation with TNM stage and metastasis in NSCLC patients. FGD5-AS1 knockdown decreased the viability, migration, and invasion of NSCLC cells. Additionally, FGD5-AS1 and MACC1 were both targeted by miR-944 with the complementary binding sites at 3' UTR. In the feedback experiments, miR-944 inhibition or MACC1 overexpression reversed the reduction effect of FGD5-AS1 knockdown on the tumorigenesis of NSCLC. Moreover, silencing of FGD5-AS1 suppressed macrophages M2 polarization, and eliminated the promoting effects of exosomes mediated macrophages on NSCLC cell migration and invasion.ConclusionsFGD5-AS1 knockdown attenuated viability, migration, and invasion of NSCLC cells by regulating the miR-944/MACC1 axis, providing a new therapeutic target for NSCLC.
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Project description:Cytochrome P450 3A5 (CYP3A5) maintains primary roles in toxic metabolism, catalyzes redox reaction, and contributes to chemotherapeutic resistance. However, the mechanism of CYP3A5 in carcinogenesis remains largely undefined. Here, we investigated a novel role of CYP3A5 inhibiting the metastasis in lung adenocarcinoma (LUAD) via ATOH8/Smad1 axis. We found that CYP3A5 was generally down-regulated in LUAD by RT-PCR, western blot and immunohistochmeistry (IHC) in tissues and cell lines. Low expression of CYP3A5 was significantly associated with poor prognosis of LUAD patients. Functionally, ectopic expression of CYP3A5 could substantially inhibit the migration and invasion in vitro. Consistently, up-regulation of CYP3A5 dramatically suppressed metastatic ability in vivo. Mechanistically, high-throughput phosphorylation chip indicated that CYP3A5 significantly decreased the phosphorylation of Smad1, resulting in suppression of metastasis. Furthermore, bioinformatics analysis and co-immunoprecipitation (Co-IP) experiments uncovered that CYP3A5 interacted with ATOH8, and the interaction, in turn, mediated in-activation in the Smad1 pathway. The combined IHC panel, including CYP3A5 and phosphorylation of Smad1, exhibited a better prognostic value for LUAD patients than any of these components individually. Taken together, CYP3A5 repressed activation of Smad1 to inhibit LUAD metastasis via interacting with ATOH8, indicating a novel potential mechanism of CYP3A5 in LUAD progression.
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Project description:BackgroundLong non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) plays a crucial role in non-small cell lung cancer (NSCLC). Nonetheless, regulatory effects of PVT1 on functions of NSCLC cells remain blurry.MethodsRelative expression levels of PVT1, miR-551b and FGFR1 mRNA in tumor tissues and cells were examined employing quantitative real-time polymerase chain reaction (qRT-PCR); CCK-8 and BrdU assays were utilized for measuring cell viability and proliferation of H1299 and A549 cells; cell migration and invasion were detected deploying Transwell assay; dual-luciferase assay was used for the validation of binding sequence between PVT1 and miR-551b. FGFR1 expression in protein level was quantified employing Western blot.ResultsPVT1 was highly expressed in NSCLC tissues and cell lines, whereas miR-551b expression was down-regulated. Overexpression of PVT1 potentiated viability, proliferation, migration and invasion of NSCLC cells while miR-551b inhibited the biological behaviors mentioned above. MiR-551b was predicted and then confirmed as a direct downstream target of PVT1. Meanwhile, a negative correlation was observed between PVT1 expression and miR-551b expression in NSCLC tissues. Besides, PVT1 could increase FGFR1 expression by repressing miR-551b expression.ConclusionPVT1 promotes the proliferation, migration and invasion of NSCLC cells by indirectly mediating FGFR1 via targeting miR-551b.
| S-EPMC8180410 | biostudies-literature
Project description:BackgroundLong non-coding RNA (lncRNA) MCM3AP-AS1 plays an oncogenic role in several malignancies, but its role in endometrioid carcinoma (EC) is unclear. This study was carried out to explore the role of MCM3AP-AS1 in EC.MethodsA total of 60 EC patients were enrolled in this study. Expression levels of MCM3AP Antisense RNA 1 (MCM3AP-AS1), microRNA-126 (miR-126), and vascular endothelial growth factor (VEGF) in tissues and transfetced cells were measured by RT-qPCR. Cell transfections were performed to explore the interaction among MCM3AP-AS1, miR-126 and VEGF. Transwell assays were perfromed to evaluate the invasion and migration abilities of HEC-1 cells after transfection.ResultsMCM3AP-AS1 was upregulated in EC and predicted poor survival. MCM3AP-AS1 directly interacted with miR-126. In EC cells, overexpression of MCM3AP-AS1 and miR-126 did not significantly affect the expression of each other. In addition, overexpression of MCM3AP-AS1 increased the expression levels of VEGF, a target of miR-126. Moreover, overexpression of MCM3AP-AS1 and VEGF increased the migration and invasion rates of EC cells, while overexpression of miR-126 suppressed these cell behaviors. Overexpression of MCM3AP-AS1 attenuated the role of miR-126 in cell invasion and migration.ConclusionsTherefore, MCM3AP-AS1 may serve as a competing endogenous RNA (ceRNA) of miR-126 to upregulate VEGF, thereby regulating cancer cell behaviors in EC.
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Project description:BackgroundAbundant evidence has manifested that long noncoding RNAs (lncRNAs) are closely implicated in human cancers, including hepatocellular carcinoma (HCC). Remarkably, lncRNA FAM83H antisense RNA 1 (FAM83H-AS1) has been reported to be a tumor-propeller in multiple cancers. However, its effect on HCC progression remains unknown.MethodsFAM83H-AS1 expression was analyzed by RT-qPCR. Colony formation, EdU, and flow cytometry as well as transwell assays were implemented to analyze the biological functions of FAM83H-AS1 on HCC progression. Luciferase reporter, RIP and RNA pull-down assays were implemented to detect the interaction among FAM83H-AS1, microRNA-485-5p (miR-485-5p), and myocyte enhancer factor 2D (MEF2D) in HCC cells.ResultsFAM83H-AS1 expression in HCC cells was markedly elevated. FAM83H-AS1 accelerated cell proliferation, migration and invasion whereas inhibiting cell apoptosis in HCC. Besides, we confirmed that FAM83H-AS1 acts as a miR-485-5p sponge in HCC cells. Additionally, MEF2D was verified to be a direct target of miR-485-5p. FAM83H-AS1 could upregulate MEF2D expression via sponging miR-485-5p. Further, rescue experiments testified that MEF2D upregulation or miR-485-5p downregulation offset the repressive effect of FAM83H-AS1 depletion on HCC cell progression.ConclusionsFAM83H-AS1 facilitates HCC malignant progression via targeting miR-485-5p/MEF2D axis, suggesting that FAM83H-AS1 may be a promising biomarker for HCC treatment in the future.
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Project description:Long non-coding RNAs (lncRNAs) are critical drivers and suppressors of human hepatocellular carcinoma (HCC). The downregulation of transmembrane protein 220 antisense RNA 1 (TMEM220-AS1) is correlated with poor prognosis in HCC. Nevertheless, the role of TMEM220-AS1 in HCC and the underlying mechanism remains unclear. In this study, TMEM220-AS1 levels were markedly reduced in HCC tissues compared with noncancerous tissues. TMEM220-AS1 downregulation was confirmed in HCC cell lines. TMEM220-AS1 expression was associated with tumor stage, venous infiltration, tumor size, and survival of HCC patients. TMEM220-AS1 overexpression suppressed the migration, invasion, and proliferation of HCC cells. Interestingly, ectopic expression of TMEM220-AS1 increased TMEM220 levels in HCC cells. Decreased TMEM220 levels were observed in HCC tissues and cell lines. TMEM220 expression was positively correlated with TMEM220-AS1 levels in HCC tissue samples and TMEM220 downregulation was significantly correlated with reduced patient survival. TMEM220 overexpression suppressed HCC cell proliferation and mobility. TMEM220 knockdown eliminated the suppressive effect of TMEM220-AS1 in HCCLM3 cells. Mechanistically, TMEM220 overexpression reduced the nuclear accumulation of β-catenin and decreased MYC, Cyclin D1, and Snail1 mRNA levels in HCCLM3 cells. BIO, a GSK3β inhibitor, eliminated TMEM220-induced Wnt/β-catenin pathway inactivation and inhibited HCC cell proliferation and mobility. In conclusion, TMEM220-AS1 and TMEM220 were expressed at low levels in HCC patients. TMEM220-AS1 inhibited the malignant behavior of HCC cells by enhancing TMEM220 expression and subsequently inactivating the Wnt/β-catenin pathway.
| S-EPMC8517989 | biostudies-literature
Project description:Non-neuronal cholinergic system is involved in lung physiology and lung cancer. However, the biochemical events downstream acetylcholine (ACh) receptor activation leading to carcinogenesis and tumor progression are not fully understood. Our previous work has shown that non-neuronal ACh acts as an autoparacrine growth factor to stimulate cell proliferation and promote epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) via activation of M2 muscarinic receptor (M2R). The aim of the present study was to delineate the underlying mechanisms linking M2R and lung tumor progression, which may provide potential therapeutic targets to delay lung cancer progression. Inhibition of M2R by antagonist or siRNA suppresses NSCLC cell migratory and invasive capacities, reverses EMT and simultaneously inactivates PI3K/Akt, MAPK ERK and NF-κB p65. On the other hand, M2R activation stimulates NSCLC migration and invasion and promotes EMT via NF-κB p65 activation. Moreover, NF-κB p65 activation induced by M2R activation was partially inhibited by either Akt or ERK inhibitor. Taken together, these results demonstrated for the first time that NF-κB p65 activation is essential in NSCLC progression associated with non-neuronal cholinergic system. Our data suggest that M2R/ERK/Akt/NF-κB axis could be a potential target for NSCLC treatment.
| S-EPMC4745730 | biostudies-literature
Project description:BackgroundIt have been proven that long non-coding RNAs (lncRNAs) serve as regulators in carcinogenesis. Interleukin enhancer binding factor 3 antisense RNA 1 (ILF3-AS1) has been illuminated as a prognostic factor in some cancers. Nevertheless, its expression pattern and possible functions in papillary thyroid carcinoma (PTC) have not been studied.MethodsThe expression of ILF3-AS1 was measured by RT-qPCR and ISH. Colony formation assay and EdU assay were used to probe cell proliferation. TUNEL assay was used for analysis of cell apoptosis. Immunofluorescence and western blot were conducted to evaluate the expression change of E-cadherin and N-cadherin. The RNA interaction was demonstrated by mechanism experiments, including pull down assay and dual luciferase reporter assay.ResultsILF3-AS1 expression was evidently upregulated in PTC cell lines. ILF3-AS1 knockdown restrained the proliferation, migration and invasion of PTC cells. Mechanical investigation revealed that miR-4306 could interact with ILF3-AS1. PLAGL2 was a downstream target of miR-4306. The effects of ILF3-AS1 knockdown on the cellular processes were abrogated by miR-4306 downregulation or pleiomorphic adenoma gene-like 2 (PLAGL2) overexpression.ConclusionILF3-AS1 plays tumor-promoting role in PTC via targeting miR-4306/PLAGL2 axis.
| S-EPMC8237480 | biostudies-literature