CircACC1 Promotes NSCLC Proliferation via miR-29c-3p/MCL-1 Signaling Pathway.
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ABSTRACT:
SUBMITTER: Zhu B
PROVIDER: S-EPMC8776987 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background:Taurine upregulated gene 1 (TUG1) has been recognized as a novel oncogenic gene. The current study was established to explore the function and regulatory mechanism of TUG1 in hepatocellular carcinoma (HCC). Methods:Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of TUG1, miR-29c-3p, and COL1A1 in tissues and cell lines. MTT assay, wound-healing and transwell assay were utilized for the detection of cell viability, migration and invasion, respectively. The interactions between miR-29c-3p and TUG1/COL1A1 were predicted by starBase v2.0 (http://starbase.sysu.edu.cn/) and verified by the dual-luciferase reporter or RNA immunoprecipitation assay. Western blot assay was performed to determine the protein levels of COL1A1, cyclin D1, E-cadherin, N-cadherin, Bcl-2, and Bax. Results:Dramatically increased expression of TUG1 was noticed in HCC tissues and cell lines. TUG1 knockdown restrained the proliferation, migration, and invasion, and promoted the apoptosis of HCC cells. TUG1 targeted miR-29c-3p and inhibited miR-29c-3p expression. Overexpression of miR-29c-3p inhibited the proliferation, migration and invasion of HCC cells. MiR-29c-3p directly targeted COL1A1 and down-regulated COL1A1 expression. In addition, downregulation of miR-29c-3p and upregulation of COL1A1 both reversed the effects of TUG1 knockdown on the proliferation, apoptosis, migration, and invasion of HCC cells. Conclusion:TUG1 could promote the proliferation, migration and invasion of HCC cells through regulating miR-29c-3p/COL1A1 axis. This novel finding might provide a latent target for the treatment of HCC.
| S-EPMC7425090 | biostudies-literature
Project description:Background In recent years, the incidence and mortality of colorectal cancer (CRC) have increased year by year among young people. Increased levels of Girdin expression predict a poor prognosis of CRC, which presents a serious threat to human health globally. Herein, we investigated the role of Girdin in CRC and explored the underlying mechanisms in CRC. Methods The expression of Girdin was detected in human specimens. HCT116 cells with stably expressing or knock-out Girdin protein were successfully constructed to observe the biological function of gene. Protein expression was determined by immunohistochemistry, immunofluorescence and western blot. Results Clinically, overexpression of Girdin was observed in the tumor tissue and poor prognosis of CRC patients. Gain-of-function and loss-of-function assays showed that Girdin promoted CRC cell proliferation in vitro. Mechanistically, Girdin knock-down significantly enhanced apoptosis, the mitochondrial membrane potential dropped, and the reactive oxygen species increased greatly. Last but not least, we analyzed the TargetScan dataset and found that Girdin was a regulated target of hsa-miR-29c-3p in CRC. Luciferase reporter assay was used to verify the interaction between hsa-miR-29c-3p and the 3’UTR of Girdin. Conclusions Our findings suggest that Girdin has a crucial role in CRC progression via miR-29c-3p/Girdin axis, highlighting Girdin as a therapeutic target for CRC.
| S-EPMC8797721 | biostudies-literature
Project description:Breast cancer (BRCA) is one of the most deadly cancers worldwide, with poor survival rates that could be due to its high proliferation. Human all-alpha dCTP pyrophosphatase 1 (DCTPP1) is implicated in numerous diseases, including cancers. However, its role in BRCA is unclear. In this study, we used bioinformatic analyses of the ONCOMINE, UALCAN, and GEPIA databases to determine the expression pattern of DCTPP1 in BRCA. We found that elevated DCTPP1 levels correlate with poor BRCA prognosis. DCTPP1 silencing inhibited BRCA cell proliferation and induced apoptosis in vitro, as well as in vivo. Our data show that this tumorigenic effect depends on DNA repair signaling. Moreover, we found that DCTPP1 is directly modulated by miR-378a-3p, whose downregulation is linked to BRCA progression. Our results showed down-regulation of miR-378a-3p in BRCA. Upregulation of miR-378a-3p, on the other hand, can inhibit BRCA cell growth and proliferation. This study shows that reduced miR-378a-3p level enhances DCTPP1 expression in BRCA, which promotes proliferation by activating DNA repair signaling in BRCA.
| S-EPMC8185175 | biostudies-literature
Project description:BACKGROUND:Increasing evidence supports the association of microRNA with tumor occurrence and development. However, the expression of miR-6875-3p and its role in cell proliferation, invasion and metastasis in hepatocellular carcinoma (HCC) remains elusive. METHODS:The expression of miR-6875-3p and BTG2 in HCC tissues and cell lines was detected by using in situ hybridization, immunohistochemistry and qRT-PCR, respectively. A western blot assay, qRT-PCR and Luciferase reporter assay were employed to study the interaction between miR-6875-3p and BTG2. Cell proliferation invasion and metastasis were measured by MTT, transwell and matrigel analyses in vitro. In vivo, tumorigenicity and metastasis assays were performed in nude mice. RESULTS:We found that miR-6875-3p were elevated expressed in HCC tissues and cell lines, and negatively correlated with BTG2 expression, while positively correlated with tumor staging, size, degree of differentiation, and vascular invasion of HCC. Moreover, in vitro and in vivo assays showed that miR-6875-3p regulates EMT and improve the proliferation, metastasis and stem cell-like properties of HCC cells. BTG2 was identified as a direct and functional target of miR-6875-3p via the 3'-UTR of BTG2. We also confirmed that miR-6875-3p plays its biological functions via the BTG2/FAK/Akt pathway. CONCLUSION:Our study provides evidence that high expression of miR-6875-3p can promote tumorigenesis of HCC in vitro and in vivo, so as to function as a novel oncogene in HCC. In mechanism, we found that miR-6875-3p plays its biological functions via the BTG2/FAK/Akt pathway.
| S-EPMC6323674 | biostudies-other
Project description:Previous studies have indicated that lung adenocarcinoma (LUAD) is one of the common human malignancies, and its incidence keeps rising. With the help of microarray technology, downregulation of miR-373-3p was observed in LUAD tissues compared with normal lung tissues. Notably, the present study demonstrated that the expression of amyloid precursor protein (APP) mRNA in LUAD tissues was overexpressed compared with adjacent tissues. Bioinformatic analysis demonstrated that miR-373-3p may interact with the 3' untranslated region of APP mRNA, and then western blot and dual-luciferase reporter gene assays were employed to verify the interaction. Finally, CCK-8 assays were used to measure the tumor-suppressing effect of miR-373-3p on A549 and it was demonstrated that overexpression of miR-373-3p may more effectively inhibit the proliferation of A549 compared with APP si-RNA. Overall, the findings suggest that miR-373-3p downregulation partly accounts for APP overexpression and leads to a promotion of cell growth in LUAD. miR-373-3p may therefore act as a valuable target in potential anticancer strategies to treat LUAD.
| S-EPMC5768135 | biostudies-literature
Project description:Long noncoding RNA (LncRNA) is a new type of regulatory RNA. LncRNA HOX antisense intergenic RNA (HOTAIR), as an oncogene in non-small cell lung cancer (NSCLC), is one of the key determinants of tumor progression. However, its possible molecular mechanism and the immunomodulatory pathway involved in NSCLC are still unclear. This study aims to explore whether HOTAIR promotes proliferation, migration and invasion of the NSCLC cells by inhibiting the expression of C-C Motif Chemokine Ligand 22 (CCL22). We collected 30 clinical samples of cancer and adjacent normal tissues from the patients with NSCLC, using real-time quantitative polymerase chain reaction (RT-qPCR) to detect the LncRNA HOTAIR and CCL22 mRNA expression in tissues. Immunohistochemistry was used to detect the protein expression of CCL22 in cancer and adjacent normal tissues. Cell experiments were conducted to verify that LncRNA HOTAIR regulates the expression of CCL22 and participates in the progress of NSCLC. The antisense oligonucleotide (ASO) probe interfering with LncRNA HOTAIR and the interference fragment of CCL22 (si-CCL22) were constructed. A549 cells were co-transfected with ASO-HOTAIR and si-CCL22. We used RT-qPCR to detect the expression of LncRNA HOTAIR and CCL22 mRNA in the cells, enzyme-linked immunosorbent assay (ELISA) used to detect the CCL22 protein level in the cell supernatant. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was applied to detect cell proliferation, the Flow cytometry to detect cell apoptosis. Finally, the Transwell test was utilized to detect cell migration and invasion. In conclusion, this study suggests that HOTAIR may promote proliferation, migration and invasion of the NSCLC cells by inhibiting CCL22 expression, which may play a key role in NSCLC cell immunity.
| S-EPMC8853541 | biostudies-literature
Project description:Background: Increasing evidence suggested that microRNA and kinesin superfamily proteins play an essential role in ovarian cancer. The association between KIF4A and ovarian cancer (OC) was investigated in this study.Methods: We performed bioinformatics analysis in the GEO database to screen out the differentially expressed miRNAs (DEmiRNAs) associated with ovarian cancer prognosis. Upstream targeting prediction for KIF4A was acquired by using the mirDIP database. The potential regulatory factor miR-29c-3p for KIF4A was obtained from the intersection of the above all miRNAs. The prognosis of KIF4A and target-miRNA in OC was obtained in the subsequent analysis. qRT-PCR and Western blot detected KIF4A expression level in IOSE80 (human normal ovarian epithelial cell line). In the meantime, the gene expression level was detected in A2780, HO-8910PM, COC1, and SKOV3 cell lines (human ovarian carcinoma cell line). MTT and colony formation assays were used to detect cell proliferation of SKOV3 cell line. The following assays detected cell migration through the use of transwell and wound heal assays. Targeted binding relationship between KIF4A and miRNA was detected by using the dual-luciferase reporter assay.Results: Both high expression of KIF4A and lower expression of miR-29c-3p could be used as biomarkers indicating poor prognosis in OC patients. Cellular function tests confirmed that when KIF4A was silenced, it inhibited the proliferation and migration of OC cells. In addition, 3'-UTR of KIF4A had a direct binding site with miR-29c-3p, which indicated that the expression of KIF4A could be regulated by miR-29c-3p. In subsequent assays, the proliferation and migration of OC cells were inhibited by the overexpression of miR-29c-3p. At the same time, rescue experiments also confirmed that the promotion of KIF4A could be reversed by miR-29c-3p.Conclusion: In a word, our data revealed a new mechanism for the role of KIF4A in the occurrence and development of OC.
| S-EPMC7709319 | biostudies-literature
Project description:Background: Lung adenocarcinoma (LUAD) is the major form of lung cancer that presents a major peril to public health. Owing to the high rates of morbidity, mortality and chemoresistance, it is necessary to develop more effective therapeutic targets of LUAD. Mitochondrial fission regulator 1 (MTFR1) affects the occurrence and development of some diseases by regulating mitochondrial dynamics and is dysregulated in LUAD. However, the functions and molecular mechanisms of MTFR1 in LUAD have not been investigated. Methods: Immunohistochemical (IHC) analysis, real-time quantitative polymerase chain reaction (RT-qPCR), bioinformatic analysis and western blot (WB) were performed to assess the expression of MTFR1 at both protein and mRNA levels. The biological functions of MTFR1 in LUAD cells were assessed based on various in vivo and in vitro experiments. The dual-luciferase reporter assay and some rescue experiments were performed to evaluate the underlying mechanism of MTFR1 in LUAD. Results: MTFR1 was upregulated in LUAD cells and tissues and correlated with dismal clinicopathologic features and a worse prognosis of patients with LUAD. Functionally, MTFR1 overexpression stimulated the proliferation, invasion, migration and glycolytic capacity and impeded the apoptosis of LUAD cells; however, opposite results were obtained when MTFR1 expression was knocked down. MTFR1, which was directly targeted by miR-29c-3p, may exert its biological functions through the AMPK/mTOR signalling pathway. Conclusion: MTFR1 promotes the progression of LUAD. Therefore, targeting MTFR1 can offer an effective therapeutic strategy for LUAD treatment.
| S-EPMC8672271 | biostudies-literature
Project description:BACKGROUND:Diabetes is associated with the dysfunction of endothelial progenitor cells (EPCs), characterized as impaired angiogenesis, a phenomenon thought to be involved in the development of diabetic foot. lncRNA plays an essential role in microvascular dysfunction and signaling pathways in patients with diabetes. lncRNA taurine upregulated gene 1 (TUG1) participates in angiogenesis in various cells. However, the mechanisms of TUG1 activity in EPCs have not been elucidated. METHODS:We isolated and then characterized EPCs from the peripheral blood of mice using immunofluorescence and flow cytometry. Western blot detected the wnt/?-catenin pathway in high glucose-treated EPCs. Bioinformatics analysis predicted a putative binding site for TUG1 on miR-29c-3p. The interactions among TUG1, platelet-derived growth factor-BB (PDGF-BB), and miR-29c-3p were analyzed by luciferase assays. In vivo, diabetic mouse ischemic limb was treated with normal saline or TUG1 overexpression lentiviruses. RESULTS:We found that EPC migration, invasion, and tube formation declined after treatment with high glucose, but improved with TUG1 overexpression. Mechanically, wnt/?-catenin pathway and autophagy were involved in the function of TUG1 overexpression in high glucose-treated EPCs. Moreover, TUG1 regulates the PDGF-BB/wnt pathway and function of high glucose-treated EPCs via miR-29c-3p. In vivo, injection of TUG1 lentivirus in a diabetic mouse ischemic limb model stimulated angiogenesis. CONCLUSIONS:Our findings suggest that TUG1 restores high glucose-treated EPC function by regulating miR-29c-3p/PDGF-BB/Wnt signaling.
| S-EPMC7558752 | biostudies-literature
Project description:BackgroundGastric cancer (GC) is one of the most frequent malignant tumors and the molecular mechanism underlying its proliferation remains far from completely understood. Although accumulating evidence shows that abnormal expression of microRNA (miRNA) is involved in tumorigenesis, the role of specific miRNAs involved in GC remains elusive. MiR-199a/b-3p functions as a tumor suppressor in diverse cancers, but its expression, function, and mechanism in GC remain unclear. Our aim is to explore miR-199a/b-3p expression and its role in regulating GC cell proliferation.MethodsReal-time PCR was performed to determine miR-199a/b-3p expression in GC tissues and normal adjacent tissues as well as normal gastric mucosal cell line GES-1 and GC cell lines MGC-803 and SGC-7901. MTT assay and Western blot were performed to determine cell proliferation and expression of PAK4, p-MEK and p-ERK, respectively. MiR-199a/b-3p mimics-transfected assay and PAK-specific siRNA assay were performed to determine their function in cell proliferation, respectively. GC xenograft nude mice were used to determine miR-199a/b-3p function in cell proliferation.ResultsMiR-199a/b-3p expression was significantly decreased in GC tissues and GC cell lines MGC-803 and SGC-7901. MiR-199a/b-3p over-expression and PAK4 silencing inhibited cell proliferation and diminished the activation of p-MEK and p-ERK in MGC-803 and SGC-7901 cells, and miR-199a/b-3p over-expression reduced PAK4 expression. MiR-199a/b-3p over-expression suppressed MGC-803 cell growth and PAK4 expression in nude mice.ConclusionsmiR-199a/b-3p inhibits GC cell proliferation via down-regulating PAK4/MEK/ERK signaling pathway and may be a novel prognostic biomarker and a potential therapeutic target for GC patients.
| S-EPMC5756398 | biostudies-literature