MicroRNA-934 promotes colorectal cancer cell proliferation by directly targeting Dickkopf-related protein 2.
Ontology highlight
ABSTRACT:
SUBMITTER: Liu W
PROVIDER: S-EPMC8343583 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Deregulation of microRNA-92b (miR-92b) has been implicated in osteosarcoma. However, the underlying regulatory mechanism of miR-92b in osteosarcoma growth and metastasis remains largely unclear. In the present study, reverse transcription-quantitative polymerase chain reaction and western blotting were used to measure mRNA and protein expression. MTT and Transwell assays were conducted to determine cell proliferation and invasion, and a luciferase reporter assay was performed to confirm the association between miR-92b and Dickkopf3-related protein (DKK3). The results demonstrated that miR-92b was significantly upregulated in osteosarcoma tissues compared with matched adjacent non-tumor tissues. Additionally, high miR-92b levels were significantly associated with lung metastasis and advanced tumor, node, metastasis stage (P<0.05) but not with age, sex, tumor size, location, serum lactate dehydrogenase or serum alkaline phosphatase. miR-92b expression was also significantly upregulated in osteosarcoma cell lines compared with normal osteoblast cells. Knockdown of miR-92b significantly inhibited the proliferation and invasion of osteosarcoma U2OS cells (P<0.01). By contrast, overexpression of miR-92b significantly increased U2OS cell proliferation and invasion (P<0.01). DKK3 was identified as a target gene of miR-92b and it was demonstrated that DKK3 expression was negatively regulated by miR-92b in U2OS cells. Restoration of DKK3 expression abrogated the increased proliferation and invasion of U2OS cells induced by miR-92b overexpression. Notably, DKK3 was significantly downregulated in osteosarcoma tissues compared with adjacent non-tumor tissues and its expression was inversely correlated to miR-92b levels in osteosarcoma tissues. Taken together, these data indicate that miR-92b promotes cell proliferation and invasion in osteosarcoma by targeting DKK3. Therefore, miR-92b may become a potential therapeutic target for osteosarcoma.
| S-EPMC5729699 | biostudies-literature
Project description:MicroRNA-92a (miR-92a) was recently reported to have an oncogenic role in cervical cancer; however, the underlying mechanism remains largely unclear. The present study aimed to investigate the expression, clinical significance and regulatory mechanism of miR-92a in cervical cancer. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) data indicated that miR-92a was significantly upregulated in cervical cancer tissues compared with matched adjacent non-tumor tissues (P<0.01). High expression of miR-92a was significantly associated with poor differentiation (P=0.031), advanced clinical stage (P=0.011) and lymph node metastasis (P=0.014), but not associated with age, tumor size and distant metastasis. Knockdown of miR-92a significantly inhibited the viability and invasion of cervical cancer HeLa cells, while overexpression of miR-92a significantly enhanced HeLa cell viability and invasion (P<0.01). Luciferase reporter assay identified Dickkopf-related protein 3 (DKK3) as a target gene of miR-92a, and the protein expression of DKK3 was negatively regulated by miR-92a in HeLa cells. Furthermore, overexpression of DKK3 significantly eliminated the stimulative effects of miR-92a on HeLa cell viability and invasion (P<0.01). Additionally, DKK3 was significantly downregulated in cervical cancer tissues compared with adjacent non-tumor tissues (P<0.01), inversely correlated to the miR-92a levels in cervical cancer tissues (P<0.01). In summary, the present study indicated that miR-92a promotes cell viability and invasion in cervical cancer, partly at least, via inhibiting the protein expression of DKK3. Therefore, the present study highlights the clinical significance of the miR-92a/DKK3 axis in cervical cancer.
| S-EPMC5526164 | biostudies-other
Project description:Renal cell carcinoma (RCC) is insensitive to conventional chemotherapy and radiotherapy, and its prognosis remains poor. Targeted therapy is a novel technique for the treatment of RCC. The present study aimed to determine the precise effects of microRNA-183 (miR-183) on RCC. Reverse transcription-quantitative polymerase chain reaction analysis was conducted in order to analyze the expression level of miR-183 in RCC cell lines. Cell transfection, viability assays and invasion assays were also performed, followed by western blot analysis and a luciferase reporter assay, in order to examine the effects of miR-183. The expression of miR-183 was upregulated in all four RCC cell lines compared with the immortalized normal proximal tubule epithelial HK-2 cell line. The cell viability and invasion assays demonstrated that decreased expression of miR-183 suppressed RCC cell proliferation and invasion in vitro. Furthermore, the present study identified that Dickkopf-related protein-3 (DKK-3) was a direct target of miR-183 in RCC. The results demonstrated that miR-183 functioned as an oncogene by downregulating DKK-3 expression and that it provided a potential diagnostic, prognostic and therapeutic target for RCC.
| S-EPMC5840664 | biostudies-literature
Project description:Colorectal cancer (CRC), one of the most common cancer types, causes a large number of cancer?related mortalities annually worldwide. Dysregulated microRNAs (miRNAs/miR) are closely associated with the malignant progression of CRC. Therefore, the present study aimed to investigate the expression and regulatory role of miR?592 in CRC. It was found that miR?592 expression was significantly elevated in CRC tissues and cell lines, and was associated with the prognosis of patients. Cellular phenotype assays demonstrated that miR?592 could promote CRC cell proliferation, migration and invasion. Bioinformatics analysis demonstrated that miR?592 mainly participated in the positive regulation of transcription, as well as the regulation of cell motility. Moreover, miR?592 targets were enriched in several signaling pathways, such as the 'mTOR' and 'FoxO' signaling pathways. In addition, secreted protein acidic and rich in cysteine (SPARC) was identified as a target of miR?592 in CRC. The present results suggested that miR?592 acts as an oncogene in CRC, in part, by directly inhibiting SPARC expression. Collectively, the present study provides a novel potential therapeutic strategy for CRC.
| S-EPMC7893699 | biostudies-literature
Project description:Inactivation of the tumor suppressor protein Merlin leads to the development of benign nervous system tumors in neurofibromatosis type2 (NF2). Documented causes of Merlin inactivation include deleterious mutations in the encoding neurofibromin2 gene (NF2) and aberrant Merlin phosphorylation leading to proteasomal degradation. Rare somatic NF2 mutations have also been detected in common human malignancies not associated with NF2, including colorectal and lung cancer. Furthermore, tumors without NF2 mutations and with unaltered NF2 transcript levels, but with low Merlin expression, have been reported. The present study demonstrated that NF2 is also regulated by microRNAs (miRNAs) through direct interaction with evolutionarily conserved miRNA response elements (MREs) within its 3'?untranslated region (3'UTR). Dual?Luciferase assays in human colorectal carcinoma (HCT116) and lung adenocarcinoma (A549) cells revealed downregulation of NF2 by miR?92a?3p via its wild?type 3'UTR, but not NF2?3'UTR with mutated miR?92a?3p MRE. HCT116 cells overexpressing miR?92a?3p exhibited significant downregulation of endogenous NF2 mRNA and protein levels, which was rescued by co?transfection of a target protector oligonucleotide specific for the miR?92a?3p binding site within NF2?3'UTR. miR?92a?3p overexpression in HCT116 and A549 cells promoted migration, proliferation and resistance to apoptosis, as well as altered F?actin organization compared with controls. Knockdown of NF2 by siRNA phenocopied the oncogenic effects of miR?92a overexpression on HCT116 and A549 cells. Collectively, the findings of the present study provide functional proof of the unappreciated role of miRNAs in NF2 regulation and tumor progression, leading to enhanced oncogenicity.
| S-EPMC6412542 | biostudies-literature
Project description:Glioma is one of the deadliest malignant brain tumors in adults worldwide. MicroRNA (miR) has been reported to be a pivotal regulator in human tumors. The aim of this study was to determine the expression, function, and mechanism of action of miR-1269a in glioma progression. The expression of miR-1269a was higher in both glioma cases reported in databases and glioma cell lines, and it was highly associated with poorer prognosis. Next, it was shown in vitro that mimic of miR-1269a could promote glioma progression and arrest apoptosis, whereas the inhibition of miR-1269a exhibited the opposite effects. In addition, miR-1269a was found to directly target ATRX chromatin remodeler by a dual-luciferase reporter assay. Moreover, ATRX overexpression could reverse the suppressive effects of miR-1269a on proliferation and apoptosis in vitro. In vivo subcutaneous xenograft tumor assay was also performed to confirm the phenotypes and molecular mechanism involved. Taking the findings together, our study implies that the miR-1269a/ATRX axis is a novel therapeutic target of glioma.
| S-EPMC7659443 | biostudies-literature
Project description:Background:MicroRNAs (miRNAs) are important regulators for cancer cell proliferation. miR-585 has been shown to inhibit the proliferation of several types of cancer, however, little is known about its role in human glioma cells. Methods:miR-585 levels in human glioma clinical samples and cell lines were examined by quantitative real-time PCR (qRT-PCR) analysis. Cell proliferation was measured by Cell Counting Kit-8 (CCK-8) and EdU incorporation assays in vitro. For in vivo investigations, U251 cells were intracranially inoculated in BALB/c nude mice and xenografted tumors were visualized by magnetic resonance imaging (MRI). Results:miR-585 expression is downregulated in human glioma tissues and cell lines compared with non-cancerous counterparts. Additionally, miR-585 overexpression inhibits and its knockdown promotes human glioma cell proliferation in vitro. Moreover, miR-585 overexpression also inhibits the growth of glioma xenografts in vivo, suggesting that miR-585 may act as a tumor suppressor to inhibit the proliferation of human glioma. Furthermore, miR-585 directly targets and decreases the expression of oncoprotein murine double minute 2 (MDM2). More importantly, the restoration of MDM2 via enforced overexpression markedly rescues miR-585 inhibitory effect on human glioma cell proliferation, thus demonstrating that targeting MDM2 is a critical mechanism by which miR-585 inhibits human glioma cell proliferation. Conclusions:Our study unveils the anti-proliferative role of miR-585 in human glioma cells, and also implicates its potential application in clinical therapy.
| S-EPMC7523344 | biostudies-literature
Project description:Lung cancer is the most common cause of cancer- associated mortality for men and women worldwide. An increasing number of studies have reported that the abnormal expression of microRNAs contributes to the pathogenesis of the majority of human cancer types, including non-small cell lung cancer (NSCLC). The present study aimed to measure microRNA-650 (miR-650) expression in NSCLC and evaluate its function in NSCLC cells. Reverse transcription-quantitative polymerase chain reaction was used to determine miR-650 expression in NSCLC tissue samples and cell lines. Assays for cell proliferation, migration and invasion were performed to investigate the roles of miR-650 on NSCLC progression. Furthermore, the mechanisms underlying the effects of miR-650 on NSCLC cell growth and metastasis were determined. In the current study, miR-650 was demonstrated to be highly expressed in NSCLC tissue samples and cell lines. Inhibition of expression of miR-650 suppressed NSCLC cell proliferation, migration and invasion in vitro. Additionally, large tumor suppressor kinase 2 (LATS2) was identified as a direct target gene of miR-650 in NSCLC. LATS2 was revealed to be significantly downregulated in NSCLC tissues and was negatively correlated with miR-650 expression. Notably, LATS2 re-expression decreased NSCLC cell proliferation, migration and invasion; similar to the effects induced by miR-650 underexpression. In conclusion, the results of the current study suggest that miR-650 may serve as an oncogene by direct targeting LATS2 in NSCLC formation and progression.
| S-EPMC5488734 | biostudies-literature
Project description:BackgroundIncreasing evidence has indicated that microRNAs (miRNAs) are strongly implicated in the initiation and progression of glioblastoma multiforme (GBM). Here, we identified a novel tumor suppressive miRNA, miR-377, and investigated its role and therapeutic effect for GBM.MethodsMiRNA global screening was performed on GBM patient samples and adjacent nontumor brain tissues. The expression of miR-377 was detected by real-time reverse-transcription PCR. The effects of miR-377 on GBM cell proliferation, cell cycle progression, invasion, and orthotopic tumorigenicity were investigated The therapeutic effect of miR-377 mimic was explored in a subcutaneous GBM model. Western blot and luciferase reporter assay were used to identify the direct and functional target of miR-377.ResultsMiR-377 was markedly downregulated in human GBM tissues and cell lines. Overexpression of miR-377 dramatically inhibited cell growth both in culture and in orthotopic xenograft tumor models, blocked G1/S transition, and suppressed cell invasion in GBM cells. Importantly, introduction of miR-377 could strongly inhibit tumor growth in a subcutaneous GBM model. Subsequent investigation revealed that specificity protein 1 (Sp1) was a direct and functional target of miR-377 in GBM cells. Silencing of Sp1 recapitulated the antiproliferative and anti-invasive effects of miR-377, whereas restoring the Sp1 expression antagonized the tumor-suppressive function of miR-377. Finally, analysis of miR-377 and Sp1 levels in human GBM tissues revealed that miR-377 is inversely correlated with Sp1 expression.ConclusionThese findings reveal that miR-377/Sp1 signaling that may be required for GBM development and may consequently serve as a therapeutic target for the treatment of GBM.
| S-EPMC4201073 | biostudies-literature
Project description:Glioma is one of the most common, rapidly progressive and fatal brain tumors, and accumulating evidence shows that microRNAs (miRNAs) play important roles in the development of cancers, including glioma. Therapeutic applications of miRNAs in Ras-driven glioma have been proposed; however, their specific functions and mechanisms are poorly understood. Here, we report that miR-1301-3p directly targets the neuroblastoma Ras viral oncogene homolog (N-Ras) and functions as a tumor-suppressor in glioma. Quantitative reverse transcription-PCR was applied to detect the expression of miR-1301-3p in glioma specimens. The direct target genes of miR-1301-3p were predicted by bioinformatic analysis and further verified by immunoblotting and luciferase assays. The effects of miR-1301-3p on the proliferation and cell cycle of glioma cells were analyzed by cell-counting kit 8, colony formation, 5-ethynyl-2-deoxyuridine (EDU) and flow cytometry assays. A xenograft model was used to study the effect of miR-1301-3p on tumor growth and angiogenesis. The expression levels of miR-1301-3p in glioma specimens were significantly downregulated. N-Ras was confirmed as a direct target of miR-1301-3p. MiR-1301-3p inhibited glioma cell growth and blocked the cell cycle to G1 by negatively regulating N-Ras and its downstream signaling pathway, MEK-ERK1/2. Furthermore, the inhibitory effects of miR-1301-3p could be rescued by the overexpression of N-Ras. The protein levels of N-Ras were up-regulated in clinical glioma specimens and were negatively correlated with miR-1301-3p expression levels (r=-056, P=0.0002). In vivo studies revealed that increased levels of miR-1301-3p delayed the growth of intracranial tumors, which was accompanied by decreased Ki67 and CD31 expression. Taken together, our results demonstrate that miR-1301-3p plays a significant role in inactivating the Ras signaling pathway through the inhibition of N-Ras, which may provide a novel therapeutic strategy for treatment of glioma and other Ras-driven cancers.
| S-EPMC5411805 | biostudies-other