Long intergenic noncoding RNA00265 promotes proliferation of gastric cancer via the microRNA-144-3p/Chromobox 4 axis.
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ABSTRACT:
SUBMITTER: Yang Z
PROVIDER: S-EPMC8291797 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundLung cancer is the most common malignancy in the world and a growing number of researches have focused on its metabolic characteristics. Studies have shown that the long non-coding RNA (lncRNA) HOXA11-AS is aberrantly expressed in many tumors. However, the role of HOXA11-AS in lung adenocarcinoma (LUAD) glycolysis and other energy metabolism pathways has not been characterized.MethodThe mRNA levels of HOXA11-AS, microRNA-148b-3p (miR-148b-3p), and pyruvate kinase M2 (PKM2) were detected using qRT-PCR. The expression levels of proteins were measured using immunohistochemistry and western blot. The CCK-8, EdU, and colony formation assays were used to assess proliferation. Glycolytic changes were assessed by measuring lactate production, ATP production, and 18 F-FDG uptake. Bioinformatics analysis and dual-luciferase reporter assays were used to characterize the relationship between HOXA11-AS, miR-148b-3p, and PKM2. Proliferation and glycolytic changes were analyzed in xenograft tumor experiments using Micro-PET imaging after downregulation of HOXA11-AS in vivo.ResultsThe expression of HOXA11-AS was markedly increased in LUAD, and was strongly associated with a poor prognosis. In addition, HOXA11-AS promoted proliferation and glycolysis in LUAD, and miR-148b-3p inhibited proliferation and glycolysis in LUAD. Mechanistically, HOXA11-AS positively regulated PKM2 expression by binding to miR-148b-3p, thereby promoting LUAD proliferation and glycolysis. In addition, HOXA11-AS inhibited LUAD xenograft growth and glycolysis via upregulation of miR-148b-3p expression and downregulation of PKM2 expression in vivo.ConclusionsThese results showed that HOXA11-AS enhanced LUAD proliferation and glycolysis via the miR-148b-3p/PKM2 axis. The findings in this paper expanded our understanding of the molecular mechanisms of LUAD tumorigenesis and glycolysis and showed that HOXA11-AS could be useful as a diagnostic and prognostic marker for LUAD. 18 F-FDG PET/CT can be used to visually evaluate the therapeutic effect of targeting HOXA11-AS.
| S-EPMC9972162 | biostudies-literature
Project description:Background Therapy for patients with liver cancer in the advanced stage remains a great challenge, and there are very few approved treatments. Although accumulated evidence demonstrates the importance of lncRNAs in liver cancer, data on the functional roles and molecular mechanisms of endogenous bornavirus-like nucleoprotein (EBLN3P) have been rarely reported. Materials and Methods The bioinformatics prediction software ENCORI was used to predict the putative binding sites of EBLN3P. The regulatory roles of EBLN3P and miR-144-3p in cell proliferation, migration and invasion ability were verified by the Cell Counting Kit-8, wound healing and Transwell assays, respectively. The interactions among EBLN3P, miR-144-3p and DOCK4 were explored by a luciferase assay and Western blotting. The expression of EBLN3P and microRNA (miR)-144-3p in liver cancer tissues was quantified by reverse transcription-quantitative PCR, and the expression of dedicator of cytokinesis 4 (DOCK4) was quantified by immunohistochemical analysis. Results The present results revealed that overexpression of EBLN3P or knockdown of miR-144-3p promoted liver cancer cell proliferation, migration and invasion. Bioinformatics analysis and a luciferase assay demonstrated that EBLN3P directly interacts with miR-144-3p to attenuate miR-144-3p binding to the 3?-untranslated region of DOCK4. Furthermore, the mechanistic investigations showing that the miR-144-3p/DOCK4 regulatory loop was activated by knockdown of miR?144-3p or overexpression of DOCK4 validate the roles of EBLN3P in promoting liver cancer cell proliferation, migration and invasion in vitro. Elevated levels of EBLN3P and DOCK4 and decreased miR-144-3p expression were observed in both liver cancer tissues and cell lines. Conclusion The present study is the first to demonstrate that EBLN3P may act as a ceRNA to modulate DOCK4 expression by competitively sponging miR-144-3p, leading to the regulation of liver cancer progression, which provides new insights for liver cancer diagnosis and treatment.
| S-EPMC7532886 | biostudies-literature
Project description:Long noncoding RNAs (lncRNAs) have been investigated in multiple human cancers including gastric cancer (GC). Our research aims to explore the role of H19 in aerobic glycolysis, proliferation, and immune escape of GC cells. The expression of H19 in GC samples was analyzed using Gene Expression Profiling Interactive Analysis, Gene Expression Omnibus data, and real-time quantitative PCR analysis. Relative quantification of glucose consumption and lactate production from cell supernatant were applied to assess the aerobic glycolysis of GC cells. Subcellular fractionation, luciferase reporter, and western blot assays certified the binding between genes. Cell Counting Kit-8 and colony formation assays were used to determine GC cell proliferation. Flow cytometry, ELISA, and real-time quantitative PCR assays were applied to analyze the immunosuppressive effect of H19. H19 was highly expressed in samples of patients with GC, and associated with tumor growth in vivo. H19 knockdown suppressed glucose consumption, lactate production, and proliferation of GC cells by regulating the microRNA (miR)-519d-3p/lactate dehydrogenase A (LDHA) axis. Both miR-519d-3p depletion and LDHA overexpression could reverse the H19 knockdown-induced decrease in aerobic glycolysis and proliferation. Moreover, conditioned medium from stable knockdown H19 GC cells modulated the activity of immune cells including γδT cells, Jurkat cells, and tumor-associated macrophages in a miR-519d-3p/LDHA/lactate axis-dependent manner. The H19/miR-519d-3p/LDHA axis mainly contributed to aerobic glycolysis, proliferation, and immune escape of GC cells.
| S-EPMC8177792 | biostudies-literature
Project description:ObjectiveThis study explores LncRNA TM1-3P effects on the proliferation, apoptosis, and inflammatory response of fibroblasts in osteoarthritis (OA) and its underlying mechanism.MethodsBioinformatics was performed to analyze OA disease-related genes, miRNA profiles, and function. The targeted regulation of LncRNA TM1-3P and miR-144-3p, ONECUT2 and miR-144-3p were analyzed by dual luciferase reporter gene assay, RNA Binding Protein Immunoprecipitation (RIP), and RNA pull down. Histopathological morphology of the knee joint was observed by hematoxylin-eosin (HE) and Annona Red O/Fast Green. The expressions of mRNAs and proteins were detected by RT-qPCR, Western blot, and immunohistochemistry. Unpaired T test was used between groups, and the one-way analysis of variance of repeated measurement data was applied for multi-group comparison, following Tukey's post-test.ResultsONECUT2 and Smurf2 genes were significantly elevated in the osteoarthritis group compared with the normal group (P < 0.001, P < 0.001). Expressions of ONECUT2 and LncRNA TM1-3P were increased, and expression of miR-144-3p was decreased in interleukin (IL)-1β-induced human fibroblast synovial cells (hFSCs) (mRNA: 1.06 ± 0.24 vs. 3.29 ± 0.73, proteins: 0.22 ± 0.03 vs. 0.46 ± 0.22, 1.23 ± 0.22 vs. 3.76 ± 0.73, 1.06 ± 0.25 vs. 0.37 ± 0.13, P < 0.01, P < 0.001, P < 0.01, P < 0.05). Overexpression of miR-144-3p down-regulated the ONECUT2 expression, reduced cell proliferation, promoted apoptosis in hFSCs induced by IL-1β (mRNA: 0.89 ± 0.14 vs. 0.15 ± 0.01, P < 0.05; proteins: 0.46 ± 0.01 vs. 0.23 ± 0.01, P < 0.001; CCK8: 1.88 ± 0.07 vs. 1.65 ± 0.07; P < 0.05; EDU: 55.82 ± 1.44 vs 40.57 ± 2.24, P < 0.05; apoptosis: 10.57 ± 0.79 vs 16.36 ± 0.35, P < 0.0001). Overexpression of LncRNA TM1-3P up-regulated the expression of ONECUT2, promoted cell proliferation, and inhibited apoptosis (mRNA: 0.9 ± 0.09 vs 1.94 ± 0.12, P < 0.05; proteins: 0.61 ± 0.05 vs 0.76 ± 0.03, P > 0.05; CCK8: 2.07 ± 0.05 vs 2.47 ± 0.06; P < 0.01; EDU: 52.67 ± 1.17 vs 60.06 ± 3.24, P < 0.05; apoptosis: 10.57 ± 0.79 vs 16.36 ± 0.35, P < 0.001), which were reversed by the overexpression of miR-144-3p treatment (mRNA: 1.82 ± 0.07 vs 0.31 ± 0.07, P < 0.0001; proteins: 0.74 ± 0.02 vs 0.35 ± 0.01, P < 0.01; CCK8: 2.41 ± 0.01 vs 1.67 ± 0.02; P < 0.0001; EDU: 66.85 ± 2.86 vs 44.68 ± 1.97, P < 0.0001; apoptosis: 7.19 ± 0.19 vs 13.36 ± 0.53, P < 0.0001). Silencing LncRNA TM1-3P attenuated the injury of knee joint tissue, down-regulated the expression of ONECUT2, Smurf2, IL-1β, IL-6, TNF-α, and improved the expression of Rap1 in rats (0.71 ± 0.04 vs 0.48 ± 0.02, 0.68 ± 0.06 vs 0.36 ± 0.02, 0.74 ± 0.03 vs 0.49 ± 0.04, 0.78 ± 0.01 vs 0.54 ± 0.03, 0.68 ± 0.02 vs 0.4 ± 0.04, 0.24 ± 0.01 vs 0.4 ± 0.03, P < 0.05, P < 0.05, P < 0.05, P < 0.01, P < 0.01, P < 0.05).ConclusionLncRNA TM1-3P improved inflammation and damage of knee joints in OA rats through miR-144-3p/ONECUT2 axis, providing a new theoretical basis for gene therapy of OA.
| S-EPMC9627084 | biostudies-literature
Project description:Topoisomerase II alpha (TOP2A) is an important nuclear protein which is found in various types of cancers. Whether TOP2A plays an important role in hepatocellular carcinoma (HCC) remains unclear. Through bioinformatic analysis and clinical specimen verification, we found that TOP2A is highly expressed in HCC and is associated with poor prognosis. Knockdown and overexpression of TOP2A can respectively inhibit or promote proliferation, metastasis and invasion of HCC cells in vitro and in vivo. Mechanismly, TOP2A activates cell cycle progression from G2 to M phase by inhibiting the phosphorylation of CHK1 and promotes Epithelial-to-mesenchymal transition (EMT) process. We further confirmed that TOP2A is a direct target of miR-144-3p whose overexpressing can partially reverse the effect of TOP2A in HCC cells. Our data suggested that TOP2A functions by promoting the proliferation, migration, invasion and EMT process of HCC and can be considered as a potential target for the treatment of HCC.
| S-EPMC8771514 | biostudies-literature
Project description:BackgroundLong noncoding RNAs (lncRNAs) play a central role in the pathogenesis of various tumors, including hepatocellular carcinoma (HCC). TMPO antisense RNA 1 (TMPO-AS1) has been reported in many tumors. Nevertheless, the underlying mechanism whereby TMPO-AS1 influences HCC remains unclear. Our research aimed to reveal the molecular mechanism governing the function of TMPO-AS1 in HCC.MethodsTMPO-AS1 expression levels in HCC tissues/cells were evaluated using reverse transcriptase-polymerase chain reaction. The effect of TMPO-AS1 on the progression of HCC was observed by Cell Counting Kit-8 (CCK8), clone formation, wound healing, and transwell. The direct interaction between TMPO-AS1 and microRNA (miR)-126-3p was observed using a dual-luciferase reporter.ResultsWe found TMPO-AS1 expression to be remarkably higher in HCC specimens and associated with poor prognosis. Silencing of TMPO-AS1 not only inhibited HCC cell proliferation but also significantly reduced epithelial-to-mesenchymal transition-induced invasion and migration to a remarkable degree. According to the results from the online database analysis tools implemented to identify if TMPO-AS1 could target miR-126-3p, we found that miR-126-3p had a negative relationship with TMPO-AS1 in HCC specimens. Meanwhile, the luciferase reporter assay confirmed that TMPO-AS1 could directly act on miR-126-3p. Moreover, the silencing of miR-126-3p dramatically abolish the inhibitive influence of sh-TMPO-AS1 on HCC development.ConclusionsOur research demonstrated that TMPO-AS1 acts as a sponge for the tumor suppressor miR-126-3p in HCC and promotes the expression of LRP6 indirectly. Taken together, our results show that TMPO-AS1 may be regarded as a novel therapeutic target in the treatment of liver cancer.
| S-EPMC8667144 | biostudies-literature
Project description:In our previous studies, enhancer of zeste homolog 2 (EZH2) has been proven to be a key oncogenic driver in oral squamous cell carcinoma (OSCC). However, the regulatory mechanisms on EZH2 remain poorly understood in OSCC. Here, through multi-transcriptomics, bioinformatics analysis, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), the co-expression network of long noncoding RNA RC3H2 (RC3H2), microRNA-101-3p (miR-101-3p), and EZH2 were screened and validated as a competing endogenous RNA (ceRNA) mechanism in OSCC. Silencing of RC3H2 inhibited OSCC cell proliferation, colony formation, migration, and invasion in vitro and reduced the expression of EZH2 and H3K27Me3, whereas RC3H2 overexpression significantly promoted OSCC cell growth, colony formation, migration, invasion, and xenograft tumor growth in vivo and increased the expression of EZH2 and H3K27Me3. A fluorescence in situ hybridization (FISH) assay verified that RC3H2 was predominately localized to the cytoplasm. RNA pull-down and luciferase activity assays showed that miR-101-3p was physically bound to RC3H2 as well as EZH2, and its inhibitor reversed the inhibitory effect of RC3H2 knockdown on progression of OSCC. Taken together, our findings demonstrate that RC3H2 as completive endogenous RNA sponging miR-101-3p targets EZH2 and facilitates OSCC cells' malignant behavior.
| S-EPMC7066035 | biostudies-literature
Project description:Human serum microRNAs (miRNAs) have been shown to serve as disease fingerprints for predicting survival of cancer patients. However, the roles of specific miRNAs involved in gastric cancer (GC) are largely unknown. In this study, miRNA profiling was performed on sera obtained from six patients in good- and poor-survival groups. Expression of miR-423-3p was validated by quantitative RT-PCR in another 67 GC serum samples and paired normal and cancerous gastric tissues. Luciferase reporter assays were used to identify the target gene Bcl-2-interacting mediator of cell death (Bim). As a result, between the good-survival and poor-survival groups, the expression of nine serum miRNAs was altered more than two-fold. Among these, miR-423-3p was significantly increased in the poor-survival group, and its overexpression in GC tissues predicted poor survival in 119 patients with GC. miR-423-3p was found to promote cell proliferation, migration, and invasion in cell lines and animal models. Mechanistically, knockdown of the autophagy-related gene (Atg) 7 rescued the GC-promoting effect of miR-423-3p. In conclusion, miR-423-3p activates oncogenic and Beclin-1-dependent autophagy and promotes GC progression by reducing the expression of Bim. The newly identified miR-423-3p-Bim axis might be a potential therapeutic target in GC.
| S-EPMC5383553 | biostudies-literature
Project description:Recent studies have reported that Fusobacterium nucleatum (Fn) is associated with gastric cancer (GC). Cancer-derived exosomes contain key regulatory noncoding RNAs and are a crucial medium of intercellular communication. However, the function and regulatory mechanism of exosomes (Fn-GCEx) secreted from Fn-infected GC cells remains unclear. In this study, Fn-GCEx enhanced the proliferation, migration, and invasion capacity of GC cells in vitro, as well as tumor growth and metastasis in vivo. HOTTIP was also upregulated in GC cells treated with Fn-GCEx. Moreover, knockdown of HOTTIP weakened the effects of Fn-GCEx in recipient GC cells. Mechanistically, HOTTIP promoted EphB2 expression by sponging microRNA (miR)-885-3p, thus activating the PI3K/AKT pathway in Fn-GCEx treated GC cells. Overall, Fn infection induced the upregulation of exosomal HOTTIP from GC cells that subsequently promoted GC progression through the miR-885-3p/EphB2/PI3K/AKT axis. Herein, we identify a potential molecular pathway and therapeutic target for GC.
| S-EPMC10236632 | biostudies-literature
Project description:BackgroundCircular RNAs (circRNAs) have been well documented to regulate the gene expression via sponging microRNA (miRNA) in diverse neoplasms including gastric cancer (GC).MethodsIn the present study, the expressions of circ_0001023, miR-409-3p, and plant homeodomain finger 10 (PHF10) in GC tissues were detected by qRT-PCR. Chi-square test was performed to analyze the associations between circ_0001023 and pathological parameters. Cell Counting Kit-8 assay, colony formation assay, flow cytometry, and transwell assay were adopted to detect the role of circ_0001023/miR-409-3p axis in the proliferation, apoptosis, and migration of GC cells, respectively. The targeting relationship between circ_0001023 and miR-409-3p was investigated by dual?-luciferase gene reporter gene assay. Additionally, subcutaneous xenotransplanted tumor model in nude mice was established to detect the function of circ_0001023 on GC growth in vivo.ResultsCompared with adjacent tissues, the expression of circ_0001023 was significantly upregulated and correlated with lymph node invasion and higher T stage of GC patients. It has also been proved that circ_0001023 could target miR-409-3p. Silencing circ_0001023 can impede the proliferation of GC cells and promote apoptosis, while miR-409-3p inhibitors can partially reverse the biological behavior of GC cells mentioned above. Moreover, the expression of circ_0001023 was reversely associated with miR-409-3p expression but positively correlated with PHF10, a downstream oncogene of miR-409-3p.ConclusionCollectively, it is concluded that circ_0001023 promotes the progression of GC via regulating miR-409-3p/PHF10 axis.
| S-EPMC7250310 | biostudies-literature