Downregulation of long non-coding RNA LINC00460 inhibits the proliferation, migration and invasion, and promotes apoptosis of pancreatic cancer cells via modulation of the miR-320b/ARF1 axis.
Ontology highlight
ABSTRACT:
SUBMITTER: Cheng J
PROVIDER: S-EPMC8806231 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Long non‑coding RNA 00460 (LINC00460) has been reported to be involved in the tumorigenesis of various cancer types. However, the function of LINC00460 in acute myeloid leukemia (AML) remains elusive. Therefore, the present study aimed to investigate the role of LINC00460 in AML. The expression of LINC00460 in the serum of 80 diagnosed patients with AML and 67 healthy controls was measured via reverse transcription‑quantitative polymerase chain reaction, and the results were compared with clinical features and patient outcomes. The expression of LINC00460 in 45 patients with cytogenetically normal‑AML (CN‑AML) was also assayed. Receiver operating characteristic (ROC) curves were generated to evaluate the sensitivity and specificity of serum LINC00460. In addition, the effects of LINC00460 on the viability, cell cycle distribution and apoptosis of AML cells were investigated. Bioinformatics tools were used to identify the possible mechanisms of how LINC00460 affects AML cells. It was found that the expression of LINC00460 was significantly upregulated in the serum of patients with AML and those with CN‑AML. Higher expression of serum LINC00460 was positively associated with French‑American‑British classification and cytogenetics. Furthermore, ROC curve analyses demonstrated that serum LINC00460 could differentiate patients with AML from healthy individuals with an area under the curve of 0.8488 (95% CI, 0.7697‑0.9279). The serum LINC00460 expression was also significantly decreased when the patients achieved complete remission. Kaplan‑Meier analysis indicated that patients with high serum LINC00460 expression had a shorter overall survival time compared with the low serum LINC00460 expression group. Knockdown of LINC00460 inhibited viability, while inducing cell cycle arrest and apoptosis in AML cells. LINC00460 was also a decoy of microRNA (miR)‑320b, which can further inhibit the expression of PBX homeobox 3 (PBX3). Collectively, the results suggested that LINC00460 may be applied as a potential diagnostic and prognostic biomarker for patients with AML. It was identified that LINC00460 may exert its effects, at least partly, via the miR‑320b/PBX3 axis in AML.
| S-EPMC8060808 | biostudies-literature
Project description:Purpose:Long non-coding RNAs (lncRNAs) have been reported to be involved in a variety of cancers, including glioma. However, the exact role and underlying mechanism of lncRNA AGAP2 antisense RNA 1 (AGAP2-AS1) in glioma have not yet been fully elucidated. Methods:The expression levels of AGAP2-AS1, microRNA-628-5p (miR-628-5p) and pleiotrophin (PTN) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration and invasion were detected by Cell Counting Kit-8 (CCK-8) assay, flow cytometry, transwell assay, respectively. Western blot assay was used to detect the protein level of PTN. The interaction between miR-628-5p and AGAP2-AS1 or PTN was predicted by bioinformatics software and confirmed by the dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Murine xenograft model was established to confirm the role of AGAP2-AS1 in glioma progression in vivo. Results:AGAP2-AS1 expression was upregulated in glioma tissues and cells. Knockdown of AGAP2-AS1 inhibited the proliferation, migration and invasion, but facilitated apoptosis in glioma cells. Moreover, AGAP2-AS1 could directly bind to miR-628-5p and its overexpression reversed the anti-tumor effect of miR-628-5p restoration on the progression of glioma cells. In addition, miR-628-5p directly targeted PTN and its inhibition abolished the inhibitory effect of PTN knockdown on the progression of glioma cells. Furthermore, AGAP2-AS1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-628-5p to modulate PTN expression. Besides, AGAP2-AS1 depletion reduced tumor growth by upregulating miR-628-5p and downregulating PTN. Conclusion:AGAP2-AS1 knockdown suppressed cell proliferation, migration and invasion but promoted cell apoptosis in glioma cells by regulating miR-628-5p/PTN axis, providing novel avenues for treatment of glioma.
| S-EPMC7398883 | biostudies-literature
Project description:Ovarian cancer (OC) is a frequently occurring malignant tumor in women. Increasing evidence has indicated that long non‑coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) participates in OC pathogenesis. Thus, the aim of the present study was to explore the function of NEAT1 during OC progression. The expression levels of NEAT1, microRNA (miR)‑4500 and basic leucine zipper and W2 domain‑containing protein 1 (BZW1) were assessed via reverse transcription‑quantitative PCR and western blotting. Furthermore, cell proliferation, colony formation, apoptosis, migration and invasion were assessed using Cell‑Counting Kit 8, colony formation, flow cytometry and Transwell assays, respectively. Cell glycolysis was analyzed using an XF96 metabolic flux analyzer, and the relationship between miR‑4500 and NEAT1 or BZW1 was verified via dual‑luciferase reporter and RNA binding protein immunoprecipitation assays. miR‑4500 expression levels were low, whereas NEAT1 expression levels were high in OC tissues and cell lines compared with control tissues and cell lines. Moreover, the results indicated that NEAT1 was a sponge of miR‑4500, which directly targeted BZW1. NEAT1 knockdown induced OC cell apoptosis, and inhibited OC cell proliferation, colony formation, migration, invasion and glycolysis. miR‑4500 inhibitor reversed NEAT1 knockdown‑mediated effects. Similarly, miR‑4500 mimic‑mediated effects on cell functions were reversed by BZW1 overexpression. In addition, the results indicated that BZW1 expression was regulated by NEAT1 and miR‑4500. Collectively, the present study suggested that NEAT1 modulated cell proliferation, colony formation, apoptosis, migration, invasion and glycolysis via the miR‑4500/BZW1 axis in OC; therefore, NEAT1 may serve as a therapeutic target for OC.
| S-EPMC7453653 | biostudies-literature
Project description:BackgroundCircular RNAs (circRNAs) are important regulators in the pathogenesis of diseases and affects the occurrence and development of diseases. However, the role of circRNAs in osteosarcoma (OS) has not been fully elucidated.MethodsThe expression of circ_0000285, miR-409-3p and insulin-like growth factor binding protein 3 (IGFBP3) was detected using quantitative real-time PCR (qRT-PCR). The protein level of IGFBP3 was measured using western blot. CCK-8 and colony formation assays were used to determine cell proliferation. Flow cytometry was applied to measure cell cycle and cell apoptosis. Transwell assay was used to assess cell invasion and migration. Dual-luciferase reporter assay and RNA Binding Protein Immunoprecipitation (RIP) assay were performed to determine the relationship among circ_0000285, miR-409-3p and IGFBP3. The animal experiments were performed to determine the function of circ_0000285 in vivo.ResultsIn this study, we found that the expression of circ_0000285 was significantly increased in OS tissues and cells and was enriched in the cytoplasm. Knockdown of circ_0000285 inhibited OS growth in vitro and in vivo. Moreover, miR-409-3p was a target miRNA of circ_0000285 and miR-409-3p targets to IGFBP3 in OS. Besides, circ_0000285 could promote proliferation, migration, invasion and inhibit apoptosis of osteosarcoma by miR-409-3p/IGFBP3 axis.ConclusionIn this study, circ_0000285 regulated proliferation, migration, invasion and apoptosis of OS cells by miR-409-3p/IGFBP3 axis, implying that circ_0000285 was a potential target for OS therapy.
| S-EPMC7539413 | biostudies-literature
Project description:The present study aimed to investigate the potential role of long non-coding RNA growth arrest-specific transcript 5 (lncRNA GAS5) in the progression of esophageal squamous cell carcinoma (ESCC) and to reveal its possible regulatory mechanism. The expression of lncRNA GAS5 in ESCC tissues and cell lines was analyzed using reverse transcription-quantitative polymerase chain reaction and western blot analysis. The overexpression vector pc-GAS5 and control vector pc-negative control (NC), containing no GAS5 sequence, were transfected into ESCC cells. The effects of lncRNA GAS5 overexpression on cell proliferation, cell cycle distribution, cell migration and invasion were then analyzed. Besides, the expression levels of ATM-CHK2 pathway-associated proteins and epithelial-mesenchymal transition (EMT)-associated proteins were measured. Expression of lncRNA GAS5 was downregulated in the ESCC tissues compared with adjacent normal tissues, and was also downregulated in ESCC Kyse450 cells compared with the human esophageal epithelial HET-1A cell line. Additionally, lncRNA GAS5 was successfully overexpressed in ESCC cells following transfection with pc-GAS5. Overexpression of lncRNA GAS5 significantly inhibited cell proliferation, induced cell cycle arrest at G2/M phase and suppressed cellular migration and invasion. When cells were transfected with pc-GAS5, the levels of phosphorylated (p)-ATM serine/threonine protein kinase, p-checkpoint kinase 2 (CHK2), p-cell division cycle 25C, p-cyclin-dependent kinase 1, N-cadherin, vimentin and Snail were significantly increased, whereas that of E-cadherin were markedly decreased. The results of the present study indicate that overexpression of lncRNA GAS5 may inhibit cell proliferation, migration and invasion in ESCC. lncRNA GAS5 overexpression may induce cell cycle arrest at G2/M stage by activating the ATM-CHK2 pathway. The results of the current study further indicate that lncRNA GAS5 overexpression may suppress cell migration and invasion via EMT-associated proteins. lncRNA GAS5 could therefore serve as a potential target for ESCC therapy.
| S-EPMC6036321 | biostudies-literature
Project description:Impact statementExploring the molecular mechanisms of growth and function in MSCs is the key to improve their clinical therapeutic effects. Currently, more and more evidence show that the long non-coding RNA (lncRNA) plays an important role in the growth, stemness and function of MSCs.Both HULC and MALAT1 are the earliest discovered LNCRNAs, which are closely related to tumor growth. All of them can promote the growth of liver cancer stem cells. Previously, we have studied the effects of MALAT1 on the growth and function of MSCs. In this study, we focused on the effects of HULC on MSCs. We elucidated the effects of HULC on the growth and differentiation of MSCs, and explored the relationship between inflammatory stimuli and HULC expression in MSCs. Our findings provide a new molecular target for the growth and clinical application of MSCs.
| S-EPMC6434460 | biostudies-literature
Project description:Gastric cancer (GC) is a common malignant gastrointestinal tumor with high mortality. Previous study has reported that the overexpression of lncRNA HCP5 was observed in gastric cancer tissues. The purpose of this study was to investigate the molecular mechanism underlying the effect of lncRNA HCP5 on the proliferative, migratory, and invasive abilities of GC cells. The relative mRNA expression of HCP5, miR-299-3p, and SMAD5 were determined by RT-qPCR. The expressions of proteins associated with apoptosis and invasion were detected by western blot. The interaction of HCP5 with miR-299-3p and SMAD5 with miR-299-3p was confirmed by luciferase reporter assay. The cellular behaviors of AGS cells were, respectively, detected by CCK-8 assays, colony formation assays, migration and invasion assays, and flow cytometry. In our study, lncRNA HCP5 was highly expressed in GC cell lines compared with normal gastric epithelial cell. LncRNA HCP5 silencing inhibited AGS cells proliferation, migration, and invasion, while promoted cell apoptosis. Moreover, miR-299-3p downregulation could abolish the effect of HCP5 knockdown on cellular behaviors of AGS cells. Interestingly, SMAD5 is identified as the downstream target of miR-299-3p, and its expression was inhibited by miR-299-3p. More importantly, SMAD5 silencing inhibited proliferation, migration, and invasion of GC cells, and promoted cell apoptosis. In a word, lncRNA HCP5 silencing inhibits GC cell proliferation, invasion, and migration while promoting its apoptosis via regulation of miR-299-3p/SMAD5 axis. Hence, lncRNA HCP5 could be a novel and promising target for GC treatment.
| S-EPMC8806318 | biostudies-literature
Project description:It has previously been determined that long non-coding (lnc)RNA-zinc finger protein (ZNF)281 serves an oncogenic role in breast cancer; however, the role of lncRNA-ZNF281 in other cancer types is yet to be elucidated. The present study aimed to analyze the role of ZNF281 in gastric cancer by characterizing its activity in cancerous tissues and normal tissues using RT-qPCR. Overexpression experiments were also performed to investigate the interaction between ZNF281 and miR-124, and Transwell assays were conducted to analyze cell invasion and migration. The present study revealed that lncRNA-ZNF281 was upregulated, and that microRNA (miR)-124 was downregulated, in cancerous tissues compared with that in the paired adjacent healthy tissues of patients with gastric cancer. In addition, the expression levels of lncRNA-ZNF281 and miR-124 exhibited a significant inverse association. Furthermore, in vitro cell experiments determined that lncRNA-ZNF281 overexpression resulted in miR-124 inhibition, yet miR-124 overexpression did not influence lncRNA-ZNF281 expression. lncRNA-ZNF281 expression level was also associated with the clinical stage of the patient. Bioinformatics analysis revealed that lncRNA-ZNF281 may target the base pairs in the hairpin loop of the miR-124 precursor. Subsequent in vitro cell experiments indicated that lncRNA-ZNF281 overexpression resulted in promoting the migration and invasiveness of gastric cancer cells, while miR-124 over-expression led to its inhibition. In addition, miR-124 overexpression partially recovered the effects of lncRNA-ZNF281 overexpression. Therefore, lncRNA-ZNF281 may promote cancer cell migration and invasion in gastric cancer via downregulation of miR-124.
| S-EPMC7039167 | biostudies-literature
Project description:BackgroundCyclin-dependent kinase-like 1 (CDKL1) is a member of the cell division control protein 2-related serine-threonine protein kinase family. It is known to occur in various malignant tumors, but its role in neuroblastoma (NB) remains unclear.MethodsWe constructed a CDKL1-silenced NB cell strain (SH-SY5Y) and used real-time PCR and western blotting to confirm the silencing. Functional analyses were performed using the MTT, colony-formation, FACS, wound-healing and transwell invasion assays.ResultsThe expression of CDKL1 was significantly upregulated in NB tissue as compared to the adjacent normal tissue. CDKL1 knockdown significantly suppressed cell viability and colony formation ability. It also induced cell cycle G0/G1 phase arrest and apoptosis, and suppressed the migration and invasion ability of SH-SY5Y cells. CDKL1 knockdown decreased the CDK4, cyclin D1 and vimentin expression levels, and increased the caspase-3, PARP and E-cadherin expression levels in SH-SY5Y cells.ConclusionsOur findings suggest that CDKL1 plays an important role in NB cell proliferation, migration and invasion. It might serve as a potential target for NB therapy.
| S-EPMC6407201 | biostudies-literature
Project description:BackgroundLong non-coding RNA colon cancer-associated transcript 1 (CCAT1) is involved in transforming multiple cancers into malignant cancer types. Previous studies underlining the mechanisms of the functions of CCAT1 primarily focused on its decoy for miRNAs (micro RNAs). However, the regulatory mechanism of CCAT1-protein interaction associated with tumor metastasis is still largely unknown. The present study aimed to identify proteome-wide CCAT1 partners and explored the CCAT1-protein interaction mediated tumor metastasis.MethodsCCAT1-proteins complexes were purified and identified using RNA antisense purification coupled with the mass spectrometry (RAP-MS) method. The database for annotation, visualization, and integrated discovery and database for eukaryotic RNA binding proteins (EuRBPDB) websites were used to bioinformatic analyzing CCAT1 binding proteins. RNA pull-down and RNA immunoprecipitation were used to validate CCAT1-Vimentin interaction. Transwell assay was used to evaluate the migration and invasion abilities of HeLa cells.ResultsRAP-MS method worked well by culturing cells with nucleoside analog 4-thiouridine, and cross-linking was performed using 365 nm wavelength ultraviolet. There were 631 proteins identified, out of which about 60% were RNA binding proteins recorded by the EuRBPDB database. Vimentin was one of the CCAT1 binding proteins and participated in the tumor metastasis pathway. Knocked down vimetin ( VIM ) and rescued the downregulation by overexpressing CCAT1 demonstrated that CCAT1 could enhance tumor migration and invasion abilities by stabilizing Vimentin protein.ConclusionCCAT1 may bind with and stabilize Vimentin protein, thus enhancing cancer cell migration and invasion abilities.
| S-EPMC10538881 | biostudies-literature