LncRNA Bmp1 promotes the healing of intestinal mucosal lesions via the miR-128-3p/PHF6/PI3K/AKT pathway.
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ABSTRACT:
SUBMITTER: Zhuang M
PROVIDER: S-EPMC8190101 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:It has been reported that glioma has a higher morbidity and mortality than other types of malignant brain tumor. While glioma has been extensively researched, the exact molecular mechanisms of its genesis and progression have remained to be fully elucidated. In order to explore a novel glioma-associated pathway which may represent a therapeutic target, 61 pairs of tumor tissues and adjacent normal tissues of glioma patients were collected and subjected to reverse-transcription quantitative polymerase chain reaction analysis, indicating that the relative expression of microRNA (miR)-128-3p was significantly decreased in the tumor tissues. However, the expression of neuronal pentraxin 1 (NPTX1) was obviously elevated. Through a bioinformatics analysis using Targetscan and transfection experiments, it was confirmed that NPTX1 was targeted by miR-128-3p. In the U251 human glioma cell line, transfection with miR-128-3p mimics increased the levels of phosphorylated insulin receptor substrate 1 (p-IRS-1), phosphoinositide-3 kinase (PI3K) and p-AKT, as demonstrated by western blot analysis. In addition, the proliferation rate of the cells was notably decreased following transfection with miR-128-3p mimics. Conversely, transfection with miR-128-3p inhibitor significantly increased the levels of p-IRS-1, PI3K and p-AKT, accompanied by an elevated proliferation rate of the cells. Therefore, it was indicated that miR-128-3p could reversely regulate NPTX1 expression. After the expression of NPTX1 was inhibited with specific small interfering RNA, the levels of p-IRS-1, PI3K and p-AKT were obviously decreased, while the expression of miR-128-3p was not significantly changed. Overall, it was concluded that miR-128-3p suppresses glioma through the NPTX1/IRS-1/PI3K/AKT signaling pathway.
| S-EPMC6425241 | biostudies-literature
Project description:ObjectivesLong non-coding RNAs (LncRNAs) act as an indispensable role in the Preeclampsia (PE)-related trophoblast function, while its relationship with Small Nucleolar RNA Host Gene 22 (SNHG22) remains unknown. Hence, this study aimed to investigate the roles of lncRNA SNHG22 in the Preeclampsia (PE)-related trophoblasts function and the underlying mechanism.MethodNormal placentas and placentas from PE patients were collected to detect the expression of lncRNA SNHG22. Then, trophoblasts HTR-8/Svneo and JEG-3 were purchased, cultured, and treated to investigate the roles of lncRNA SNHG22 on cell migration and invasion as well as its underlying regulatory mechanism.ResultsThe SNHG22 was downregulated in PE patients, and it was found that SNHG22 overexpression could drive migration and invasion of trophoblasts, while SNHG22 depletion exerted a suppressive effect. Mechanistically, SNHG22 was validated to regulate microRNA-128-3p (miR-128-3p), and Protocadherin 11 X-Linked (PCDH11X) was identified as the target gene of miR-128-3p. Furthermore, it was found that SNHG22 acted as a promoter in the migration and invasion of trophoblast cells in a miR-128-3p/PCDH11X dependent manner, and SNHG22 silencing weakened the activation of PCDH11X-mediated PI3K/Akt signaling pathways through inhibiting miR-128-3p, thereby preventing migration and invasion of trophoblasts.ConclusionSNHG22 acted as a driver in the migration and invasion of trophoblasts and may be considered a candidate for the amelioration of PE.
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Project description:Poultry meat quality is affected by many factors, among which intramuscular fat (IMF) is predominant. IMF content affects the tenderness, juiciness, and flavor of chicken. An increasing number of studies are focusing on the functions of lncRNAs in adipocyte differentiation. However, little is known about lncRNAs associated with intramuscular adipocyte differentiation. In the present study, we focused on an up-regulated lncRNA during intramuscular adipogenetic differentiation, which we named intramuscular fat-associated long non-coding RNA (IMFNCR). IMFNCR promotes intramuscular adipocyte differentiation. In-depth analyses showed that IMFNCR acts as a molecular sponge for miR-128-3p and miR-27b-3p and that PPARG is a direct target of miR-128-3p and miR-27b-3p in chicken. High-fat and high-protein diet inhibited chicken IMFNCR level in vivo. Moreover, IMFNCR level was positively correlated with PPARG mRNA level in chicken breast muscle tissues, a vital corollary to ceRNA function. Altogether, our research showed that IMFNCR acts as a ceRNA to sequester miR-128-3p and miR-27b-3p, leading to heightened PPARG expression, and thus promotes intramuscular adipocyte differentiation. Taken together, our findings may contribute to a more thorough understanding of chicken IMF deposition and the improvement of poultry meat quality.
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Project description:Accumulating evidences indicate that long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) promotes the progression of glioma. In this study, we postulated that NEAT1 may act as a miR-128-3p sponge. Relative levels of NEAT1 and miR-128-3p expression in human glioma samples and GBM cells were detected using quantitative real-time PCR. By means of CCK-8 assays, transwell assays, and flow cytometric analysis, the biological functions of miR-128-3p and NEAT1 were investigated in U87MG and U251MG human GBM cell lines with stable miR-128-3p and NEAT1 knockdown or overexpression. The luciferase reports, RNA pull-down assay, and RNA immunoprecipitation assay were conducted to determine the relevance of NEAT1 and miR-128-3p in glioma. As a result, high expression of NEAT1 and lack of miR-128-3p were observed in glioma specimens and cells. By binding to anti-oncogene miR-128-3p in the nucleus, NEAT1 enhanced tumorigenesis and glioma development. Further experiments suggested that ITGA5 expression was increased in glioma tissues and was found to be connected with miR-128-3p. Additionally, NEAT1 facilitated ITGA5 expression via competitively binding to miR-128-3p. For this reason, ITGA5 would not be decomposed by miR-128-3p and could activate FAK signaling pathway, thereby promoting cell growth. Collectively, these results indicated that the NEAT1/miR-128-3p/ITGA5 axis was involved in glioma initiation and progression, and might offer a potential novel strategy for treatment of glioma.
| S-EPMC8497354 | biostudies-literature
Project description:Background:Accumulating studies showed that long noncoding RNAs (lncRNAs) played vital roles in cancer progression. LncRNA MIR4435-2HG was proved to act as an oncogene in various tumors. However, the underlying function of MIR4435-2HG in ovarian cancer (OC) remains unclear. Methods:The expression levels of MIR4435-2HG, miR-128-3p and cyclin-dependent kinase 14 (CDK14) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation and apoptosis in OC cells were detected by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis, respectively. Transwell assay was applied to evaluate cell migration and invasion. Wound healing assay was performed to monitor the migration rate. Western blot assay was performed to detect the protein levels of Bcl-2, Cleaved PARP, E-cadherin, Vimentin and CDK14 in OC cells. The binding sites between miR-128-3p and MIR4435-2HG or CDK14 were predicted by online tool starBase and their relationship was confirmed by dual-luciferase reporter assay, RIP assay and pull-down experiment. Results:MIR4435-2HG and CDK14 were over-expressed in OC tissues and cells. Patients with high MIR4435-2HG expression had poorer overall survival (OS) than patients with low MIR4435-2HG expression. MIR4435-2HG knockdown inhibited proliferation, invasion and migration but induced apoptosis of OC cells via miR-128-3p/CDK14 axis. In conclusion, MIR4435-2HG knockdown suppressed the progression of OC cells through downregulating CDK14 expression by the promotion of miR-128-3p.
| S-EPMC7195767 | biostudies-literature
Project description:Accumulating evidence has shown that long noncoding RNA GAS5 is a well-known tumor suppressor in the pathogenesis of a variety of human cancers. However, the detailed role of GAS5 in osteosarcoma is still largely unclear. In this study, we found that GAS5 was downregulated in human osteosarcoma tissues and cell lines compared with matched adjacent tissues and normal osteoblast cells. Overexpression of GAS5 could significantly suppress the growth and invasion of osteosarcoma cells, while downregulation of GAS5 promoted cell proliferation and invasion. We confirmed that GAS5 could directly bind with miR-23a-3p by using luciferase reporter gene and RNA immunoprecipitation and pull-down assay. Downregulation of miR-23a-3p repressed cell proliferation and invasion. Overexpression of miR-23a-3p counterbalanced the inhibition effect of GAS5 on cell proliferation and invasion. Further studies indicated that overexpression of GAS5 inhibited cell proliferation and metastasis by regulating phosphatase and tensin homolog (PTEN). PTEN was authenticated as a target of miR-23a-3p. Upregulation of GAS5 or silence of miR-23a-3p increased the level of PTEN, while downregulation of GAS5 or overexpression of miR-23a-3p suppressed the expression of PTEN. In addition, overexpression of GAS5 could neutralize the effect of downregulating PTEN on osteosarcoma cell functions. We proved that GAS5 regulated the viability and invasion of osteosarcoma cells through the PI3K/AKT pathway. Moreover, overexpression of GAS5 could inhibit tumor growth in a xenograft nude mouse model in vivo. In summary, GAS5 functions as a competing endogenous RNA, sponging miR-23a-3p, to promote PTEN expression and suppress cell growth and invasion in osteosarcoma by regulating the PI3K/AKT pathway.
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Project description:PurposeEndometriosis, a gynecological disease, is difficult to be cured. Currently, to identify more potential biomarkers for the early diagnosis of endometriosis is urgently needed. Insulin like growth factor 2 (IGF2) has been revealed to correlate with endometriosis. This research aimed to further explore the role of IGF2 and its up-stream mechanism in endometriosis.MethodsPrimary ectopic endometrial stromal cells (EESCs) were extracted from ectopic endometrial tissues which were pathological endometrial tissues resected from three patients with II-III endometriosis. Primary normal endometrial stromal cells (NESCs) were extracted from normal endometrial tissues of two patients with grade III cervical dysplasia and one patient with uterine leiomyoma III. Four endometriotic cell lines (EEC145T, hEM15A, hEM5B2, and 12Z) and normal human endometrial epithelial cells (hEECs) were purchased. Cell proliferation, migration, and invasion were evaluated through functional assays. The molecular interaction between RNAs was investigated through mechanistic analyses.ResultsWe discovered that IGF2 was upregulated in purchased endometriotic cells and primary EESC. Suppression of IGF2 hampered cell proliferation, migration, and invasion. Furthermore, insulin-like growth factor 2 antisense RNA (IGF2-AS) was uncovered to positively regulate IGF2 expression and enhanced proliferative, migratory, and invasive abilities of endometriotic cells. Mechanistically, miR-370-3p was found to bind with IGF2-AS and IGF2. IGF2-AS competitively bind with miR-370-3p to upregulate IGF2. Furthermore, IGF2-AS was revealed to activate the PI3K/AKT/mTOR signaling pathway through targeting miR-370-3p/IGF2 axis.ConclusionIGF2-AS promotes endometriotic cell growth via regulating IGF2/miR-370-3p axis and further activating PI3K/AKT/mTOR signaling pathway.
| S-EPMC9790843 | biostudies-literature
Project description:The long non‑coding RNA (lncRNA) small nucleolar RNA host gene 22 (SNHG22) has been reported as a crucial regulator in several types of human cancer. The present study evaluated the function and mechanism of SNHG22 in colorectal cancer (CRC) progression. SNHG22 expression was detected in colorectal adenoma, CRC tumor tissues (TTs) and adjacent non‑cancerous tissues (ANTs) using reverse transcription‑quantitative PCR (RT‑qPCR). The biological behaviors of SNHG22 in CRC cell lines were explored in vitro using Cell Counting Kit‑8, flow cytometry, wound scratch assay and Transwell assay, and in vivo using a nude mouse xenograft model. The interaction between SNHG22 and microRNA‑128‑3p (miR‑128‑3p), and the target genes of miR‑128‑3p were explored using online tools, RT‑qPCR, western blotting and a dual‑luciferase reporter assay. The present study revealed that SNHG22 expression was most highly expressed in TTs followed by adenoma tissues and ANTs. In addition, high SNHG22 expression levels were significantly associated with advanced clinicopathological factors and worse survival in patients with CRC. SNHG22 knockdown markedly inhibited CRC cell proliferation, apoptosis resistance, migration and invasion in vitro, and hindered tumor growth in vivo. The mechanistic study revealed that SNHG22 bound to miR‑128‑3p and attenuated its inhibitory effects on E2F transcription factor 3 (E2F3) expression levels and activity. Rescue experiments demonstrated that inhibiting miR‑128‑3p or upregulating E2F3 offset the effects of SNHG22 knockdown on CRC cells. The present findings support the existence of an interactive regulatory network involving SNHG22, miR‑128‑3p and E2F3 in CRC cell lines, indicating that the SNHG22/miR‑128‑3p/E2F3 axis may be considered a novel diagnostic and therapeutic target in CRC.
| S-EPMC8357263 | biostudies-literature
Project description:BackgroundLong non-coding RNAs (lncRNA) plasmacytoma variant translocation 1 (PVT1) has been shown to be associated with liver fibrosis. Nevertheless, the role of PVT1 in atrial fibrosis remains undefined. This study aims to elucidate the pathophysiological role of lncRNA PVT1 in the regulation of atrial fibrosis and to explore the underlying mechanism.MethodsExpression of PVT1, miR-128-sp, and Sp1 were examined in human atrial muscle tissues and angiotensin-II (Ang-II)-induced human atrial fibroblasts. Furthermore, the role of PVT1 in regulating atrial fibrosis in Ang-II-treated human atrial fibroblasts and Ang-II-induced atrial fibrosis in mice was investigated. Moreover, the interaction among PVT1, miR-128-3p, and Sp1 were examined using bioinformatics, expression correlation analysis, gain- or loss-of-function assays, RIP assays, and luciferase reporter assays. The involvement of transforming growth factor beta 1 (TGF-β1)/Smad pathway in this process was also explored.ResultsPVT1 was increased in atrial muscle tissues from AF patients and positively with collagen I and collagen III. In vitro assay revealed that PVT1 overexpression facilitated the Ang-II-induced atrial fibroblasts proliferation, collagen production, and TGF-β1/Smad signaling activation, whereas PVT1 knockdown caused the opposite effect. In vivo assay further confirmed that PVT1 knockdown attenuated the Ang-II-induced mouse atrial fibrosis. Mechanically, PVT1 acted as a sponge for miR-128-3p to facilitate Sp1 expression, thereby activating the TGF-β1/Smad signaling pathway.ConclusionLncRNA PVT1 promotes atrial fibrosis via miR-128-3p-SP1-TGF-β1-Smad axis in atrial fibrillation.
| S-EPMC6425687 | biostudies-literature
Project description:Cardiac hypertrophy is caused by cardiac volume or pressure overload conditions and ultimately leads to contractile dysfunction and heart failure. Oxytocin (OT), an endocrine nonapeptide, has been identified as a cardiovascular homeostatic hormone with anti-hypertrophic effects. However, the underlying mechanism remains elusive. In this study, we aimed to investigate the role and mechanism of OT in cardiac hypertrophy. The rats with cardiac hypertrophy induced by isoproterenol (ISO) were treated with or without oxytocin. Cardiac functional parameters were analyzed by echocardiography. The changes in cell surface area were observed using wheat germ agglutinin (WGA) or immunofluorescence staining. The expressions of cardiac hypertrophy markers (B-Natriuretic Peptide, BNP and β-myosin heavy chain, β-MHC), long non-coding RNA Growth (LcRNA) Arrest-Specific transcript 5 (lncRNA GAS5), miR-375-3p, and Kruppel-like factor 4 (Klf4) were detected by qRT-PCR. KLF4 protein and PI3K/AKT pathway related proteins were detected by Western blot. The interactions among lncRNA GAS5, miR-375-3p, and Klf4 were verified by dual-luciferase reporter assays. The findings showed that OT significantly attenuated cardiac hypertrophy, increased expressions of lncRNA GAS5 and KLF4, and decreased miR-375-3p expression. In vitro studies demonstrated that either knock-down of lncRNA GAS5 or Klf4, or over-expression of miR-375-3p blunted the anti-hypertrophic effects of OT. Moreover, down-regulation of lncRNA GAS5 promoted the expression of miR-375-3p and inhibited KLF4 expression. Similarly, over-expression of miR-375-3p decreased the expression of KLF4. Dual-luciferase reporter assays validated that lncRNA GAS5 could sponge miR-375-3p and Klf4 was a direct target gene of miR-375-3p. In addition, OT could inactivate PI3K/AKT pathway. The functional rescue experiments further identified OT regulated PI3K/AKT pathway through lncRNA GAS5/miR-375-3p/KLF4 axis. In summary, our study demonstrates that OT ameliorates cardiac hypertrophy by inhibiting PI3K/AKT pathway via lncRNA GAS5/miR-375-3p/KLF4 axis.
| S-EPMC8678504 | biostudies-literature