LncRNA SNHG15 Promotes Ovarian Cancer Progression through Regulated CDK6 via Sponging miR-370-3p
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ABSTRACT:
SUBMITTER: Wang Y
PROVIDER: S-EPMC8560251 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPancreatic cancer is an extensively concerned human malignancy around the globe, yet the potential therapeutic target remains to be further determined. MicroRNA and LncRNA have been reported to be involved in progression of pancreatic cancer, while the biological role of microRNA-574-3p (miR-574-3p) and FAM66C in pancreatic cancer development is poorly investigated.MethodsQuantitative real-time PCR (qPCR) analysis was employed to detect the expression of miR-574-3p and FAM66C in pancreatic normal or cancerous tissues and cells. The proliferative and apoptosis signaling molecules were also examined via qPCR and western blot separately. Additionally, cell proliferation and apoptosis assay were performed via CCK8, colony formation and Annexin V-FITC apoptosis assay. Interaction between miR-574-3p and FAM66C was interrogated by luciferase reporter assay and RNA immunoprecipitation. Even more, a pancreatic cancer xenograft mice assay was implemented to illustrate the coordinating role of miR-574-3p and FAM66C in pancreatic cancer proliferation.ResultsWe found that levels of miR-574-3p were significantly higher in cancer tissues and cells compared to normal (P<0.05). Remarkably, the results indicated that depletion of miR-574-3p inhibited proliferation and promoted apoptosis of human pancreatic cancer cell lines. Additionally, FAM66C was demonstrated to interact with miR-574-3p and inhibit its expression. Significantly, FAM66C was proved to act as a tumor suppressor role via inhibiting cell proliferation and promoting cell apoptosis in pancreatic cancer. Moreover, FAM66C coordinated with miR-574-3p to regulate progression of xenograft tumor in the nude mice.ConclusionsFAM66C-miR-574-3p axis mediates progression of pancreatic and might be the promising therapeutic target for pancreatic cancer patients.
| S-EPMC8798657 | biostudies-literature
Project description:BackgroundOvarian cancer (OC) is a common female reproductive malignancy with a high mortality rate. Although LAMA4 was observed to be downregulated in OC cells, its mechanism in regulating OC metastasis is still unknown. This study aimed to investigate the effect of LAMA4 and its mechanism on OC.MethodsTo achieve this aim, a microarray analysis was performed to screen out the key genes involved in OC pathogenesis. Western-blot and qRT-PCR assays were also carried out to detect protein and mRNA expressions, respectively. A luciferase reporter assay was further used to confirm the direct interaction of miR-30e-3p with MEG3, and the direct interaction of miR-30e-3p with LAMA4 mRNA. Cytological experiments (CCK8, colony formation assay, wound-healing assay etc.) were then performed to explore the roles of miR-30e-3p, MEG3, and LAMA4 in OC cells.ResultsAfter carrying out microarray analysis, LAMA4 was confirmed as a key gene associated with OC pathogenesis. Research results proved that miR-30e-3p was markedly upregulated, while MEG3 and LAMA4 were noticeably downregulated in OC tissues and cells. The overexpression of LAMA4 significantly impaired the proliferation, migration, and invasion of OC cells. However, the upregulation of MEG3 increased the expression of LAMA4 by sponging miR-30e-3p, which alleviated the malignancy of OC cells.ConclusionsObservations showed that forced LAMA4 overexpression could inhibit OC progression, which was regulated by MEG3 via sponging miR-30e-3p. The findings of this research could provide new insights into the mechanism by which MEG3 and LAMA4 exert their anti-oncogenic roles in OC progression.Trial registration Not applicable.
| S-EPMC7245736 | biostudies-literature
Project description:BackgroundLong noncoding RNA (lncRNA) LINC00922 has been reported to promote tumorigenesis of lung and breast cancer. However, the functions and mechanisms of LINC00922 in ovarian cancer (OC) remain unclarified. The current study aims to clarify the detailed functions and underlying mechanisms of LINC00922 in the progression of OC.MethodsLINC00922 expression in OC tissues and cells was identified by a comprehensive strategy of data miming, computational biology and quantitative real-time polymerase chain reaction (RT-qPCR) experiment. In vitro CCK-8, wound healing, transwell invasion, western blotting and in vivo tumorigenesis assays LINC00922 were conducted to evaluate the functions of LINC00992. Subsequently, bioinformatics technology and dual luciferase reporter assay were performed to confirm the between miR-361-3p and LINC00922 or CLDN1. Finally, rescue experiments were performed to confirm whether LINC00922 effect functions of OC cells through regulation of miR-361-3p.ResultsLINC00922 was significantly upregulated in OC tissues and cell lines, which is significantly positively corelated with the poor prognosis of patients with OC. LINC00922 knockdown inhibited proliferation and tumorigenesis of OC cells in vitro and vivo. In addition, LINC00922 knockdown suppressed migration, invasion, and EMT of OC cells in vitro. Mechanically, LINC00922 could competitively bind with miR-361-3p to relieve the repressive effect of miR-361-3p on its target gene CLDN1 in OC cells. In addition, silencing miR-361-3p promoted OC cell proliferation, migration, invasion, EMT and Wnt/β-catenin signaling, while LINC00922 knockdown inhibited Wnt/β-catenin signaling by upregulating miR-361-3p. Rescue experiments revealed that LINC00922 knockdown inhibited OC cell proliferation, migration, invasion and EMT by regulating miR-361-3p.ConclusionThis study suggested that LINC00922 could competitively bind with miR-361-3p to promote the CLDN1 expression and activate Wnt/β-catenin signaling in OC progression, which providing a promising therapeutically target for OC.
| S-EPMC8194245 | biostudies-literature
Project description:The incidence and death rate of colorectal cancer (CRC) is very high, which brings great need to understand the early molecular events of CRC. These studies demonstrate that long noncoding RNA (lncRNA) plays an important role in the occurrence and development of human cancer. Small nucleolar RNA host gene 15 (SNHG15) was recently identified as a cancer-related lncRNA. In this study, we aimed to evaluate the function and mechanism of SNHG15 in CRC. The expression of SNHG15 was detected by quantitative RT-PCR (qRT-PCR) in CRC tissues and matched noncancerous tissues (NCTs). CCK-8 assay, colony formation assay, flow cytometric analysis, and nude mouse xenograft mode were used to examine the tumor-promoting function of SNHG15 in vitro and in vivo. The binding relationship between SNHG15, miR-338-3p and the target genes of miR-338-3p were screened and identified by databases, qRT-PCR, dual luciferase reporter assay and western blot. Our results showed that SNHG15 was up-regulated in CRC tissues compared with paired NCTs (P < 0.0001). High level of SNHG15 expression predicted poor prognosis of CRC (P = 0.0051). SNHG15 overexpression could promote cell proliferation and inhibit cell apoptosis. Animal experiments showed that up-regulation of SNHG15 promoted tumor growth in vivo. The results of mechanism experiments showed that SNHG15 could bind to miR-338-3p and block its inhibition on the expression and activity of FOS or RAB14. In conclusion SNHG15 promotes cell proliferation through SNHG15/miR-338-3p/FOS-RAB14 axis in CRC.
| S-EPMC6536931 | biostudies-literature
Project description:BackgroundGiven the poor prognosis of metastatic esophageal squamous cell carcinoma (ESCC) patients, molecular mechanisms underlying the progression and metastasis of ESCC are highly desired in the scientific community. Prostate cancer associated transcript-1 (PCAT-1) is a lncRNA up-regulated in major types of cancers and is associated with the poor prognosis of cancer patients. This study aimed to understand the expression and role of PCAT-1 in the progression and metastasis of ESCC and to identify the potential lncRNA-miRNA interactions and signaling pathways underlying the mechanisms of action of PCAT-1 in ESCC.Materials and methodsGene expression levels were determined by qRT-PCR; protein levels were determined by Western blot assay; cell proliferation, invasion and migration were determined by CCK-8, Transwell invasion and wound healing assays, respectively; in vivo tumor growth was evaluated by xenograft nude mice model.ResultsOur data showed the up-regulation of PCAT-1 in different human ESCC cell lines and in clinical ESCC tissues. Knockdown of PCAT-1 in ESCC cells significantly inhibited the proliferation, invasion and migration of the cancer cells. Moreover, we showed the interactions between PCAT-1 and miR-508-3p and demonstrated that PCAT-1 was able to repress miR-508-3p expression in ESCC cells via acting as a competing endogenous RNA. Besides, Annexin A10 (ANXA10) was identified to be the downstream target of the PCAT-1 and miR-508-3p interactions.ConclusionThis study demonstrated the functional role of PCAT-1 in promoting the proliferation, invasion and migration of ESCC cells. We also identified a PCAT-1/miR-508-3p/ANXA10 axis in mediating the promoting role of PCAT-1 in the progression of ESCC. The findings provide experimental evidence to support lncRNA PCAT-1 as a potential therapeutic target of ESCC.
| S-EPMC6941610 | biostudies-literature
Project description:BackgroundLong non-coding RNA (lncRNA) SNHG5 has been found to play an important role in tumors. Nevertheless, the function and mechanism of lncRNA SNHG5 in osteosarcoma (OS) remains unclear. The purpose of this study was to investigate whether lncRNA SNHG5 can regulate the occurrence and development of OS cells.MethodsWe performed quantitative real time PCR to detect the expression of lncRNA SNHG5 in OS cells. 143B, MG63 (knockdown) and U2OS, U2R (overexpression) cell lines were chosen for the function study of SNHG5. The effect of SNHG5, miR-212-3p, and SGK3 in OS cells was explored by MTT assays, clony formation, flow cytometry, transwell assays, wound healing assays, and cell spreading assays. Quantitative real-time PCR, Western blot analysis and luciferase assays were used to detect the interaction between lncRNA SNHG5 and miR-212-3p.ResultsIn this study, knockdown of lncRNA SNHG5 suppressed the growth and metastasis of OS cells, whereas the overexpression of SNHG5 produced an opposite result. Mechanistically, lncRNA SNHG5 functions as a sponger against miR-212-3p and suppresses the miR-212-3p/SGK3 signaling pathway. Introduction of miR-212-3p mimics or inhibitors reverses SNHG5 overexpression or silences the exerted tumor promoting or suppressing effect. In addition, our results showed that the function of SNHG5 can be rescued by miR-212-3p and can regulate the growth and metastasis of OS cells via SGK3, the downstream target of miR-212-3p.ConclusionsIn summary, our study demonstrated that lncRNA SNHG5 can regulate the proliferation and metastasis of OS cells through the miR-212-3p/SGK3 axis. This axis may provide a new target for future clinical treatment.
| S-EPMC6145323 | biostudies-literature
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.
| S-EPMC6378276 | biostudies-literature
Project description:BACKGROUND:In past decades, circular RNAs (circRNAs) have achieved increasing attention because of its regulatory role in different kinds of cancers. However, how circAGFG1 regulates cervical cancer (CC) is still largely undiscovered. This study aims to evaluate the role of a novel circRNAs and related molecular mechanism in CC cells. METHODS:High or low level of circAGFG1 was detected in CC cells or normal cell line with qRT-PCR. The proliferative and migratory abilities of CC cells were assessed with loss-of function assays. The downstream miRNA and mRNA of circAGFG1 were searched out and proved by using bioinformatics analysis and mechanism experiments. Recue assays were designed to confirm the role of circAGFG1/miR-370-3p/RAF1 axis in CC cell activities. RESULTS:The levels of circAGFG1 was abundant in CC cells in comparison with normal cervical cell End1/E6E7. The inhibitory effect of decreased circAGFG1 level on the proliferative and migratory abilities of CC cells was assessed. CircAGFG1 and miR-370-3p were localized in the cytoplasm and they can interact with each other. Moreover, miR-370-3p was downregulated in CC cells. We also determined the negative effect of miR-370-3p on RAF1. CircAGFG1 could promote RAF1 expression by absorbing miR-370-3p, thereby activating RAF/MEK/ERK pathway. circAGFG1 promoted proliferation and migration of CC cells via enhancing the activity of RAF/MEK/ERK pathway by sponging miR-370-3p and further regulating RAF1. CONCLUSION:The results of this study provided new evidence that circAGFG1 acted as a vital regulator in cervical cancer proliferation and migration, giving great promise to apply it as a potential biomarker for diagnosis and therapy in CC treatment.
| S-EPMC6842182 | biostudies-literature
Project description:BackgroundLong noncoding RNAs (lncRNAs) have been reported to play a key role in the development and progression of human malignancies. FLJ33360 is an lncRNA with unknown functions. This study was designed to determine the clinical significance and mechanism of FLJ33360 in ovarian cancer.Materials and methodsThe clinical significance of FLJ33360 in ovarian cancer was determined using the Gene Expression Profiling Interactive Analysis (GEPIA) database, Kaplan-Meier Plotter database, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and statistical analysis. The regulatory relationships between FLJ33360 and miR-30b-3p were explored through bioinformatics, the Gene Expression Omnibus (GEO) database, the ArrayExpress database and meta-analysis. The possible pathways were predicted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In addition, the key target genes were identified using a protein-protein interaction (PPI) network, the Cancer Genome Atlas (TCGA) database, and correlation analysis.ResultsFLJ33360 expression was significantly downregulated in ovarian cancer tissue (P=0.0011) and was closely associated with International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.027) and recurrence (P=0.002). FLJ33360 may have potential value in detecting ovarian cancer (area under the curve =0.793). Function analysis demonstrated that FLJ33360 can act as a molecular sponge of miR-30b-3p to regulate the expression of target genes that are mainly involved in positive regulation of smooth muscle cell migration, the unsaturated fatty acid metabolic process, and positive regulation of the epithelial to mesenchymal transition. Among these target genes, BCL2 is the hub gene.ConclusionFLJ33360 is a potential biomarker for early diagnosis and prognostic assessment in ovarian cancer and may regulate the expression of genes by sponging miR-30b-3p and thus participate in the development of ovarian cancer.
| S-EPMC6560195 | biostudies-literature
Project description:DNA methylation and long noncoding RNAs (lncRNAs) exhibit an indispensable role in follicular development. However, the specific mechanisms regarding lncRNAs mediated by DNA methylation in follicular development remain unclearly. In this study, we found that inhibiting the expression of DNMT1 promoted granulosa cells (GCs) apoptosis to inhibit follicular development. A novel follicular development-associated lncRNA named inhibitory factor of follicular development (IFFD) was mediated by DNMT1 and showed to arrest follicular development by inhibiting GCs proliferation and estrogen (E2) secretion but promoting GCs apoptosis. Mechanistically, the deactivated Cas9-TET1 demonstrated that the hypomethylation in -1261/-1254 region of IFFD promoted the transcription of IFFD by recruiting SP1. IFFD induced the expression of GLI family zinc finger 1 through competitive binding miR-370, thereby up-regulating the expression of CASP3 to promote GCs apoptosis, as well as downregulating the expressions of PCNA and CYP19A1 to inhibit GCs proliferation and E2 secretion. Collectively, DNMT1-mediated IFFD might be a novel target for the regulation of follicular development.
| S-EPMC9950381 | biostudies-literature