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Small nucleolar RNAs (snoRNAs), a type of non-coding RNA, are widely present in the nucleoli of eukaryotic cells and play an important role in rRNA modification. With the recent increase in research on snoRNAs, new evidence has emerged indicating that snoRNAs also participate in tRNA and mRNA modification. Studies suggest that numerous snoRNAs, including tumor-promoting and tumor-suppressing snoRNAs, are not only dysregulated in tumors but also show associations with clinical prognosis. In this review, we summarize the reported functions of snoRNAs and the possible mechanisms underlying their role in tumorigenesis and cancer development to guide the snoRNA-based clinical diagnosis and treatment of cancer in the future.
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Circular RNAs (circRNAs) play important roles in cancer tumorigenesis and progression, representing prognostic biomarkers and therapeutic targets. In this case, we demonstrated the role of circ-NOLC1 in epithelial ovarian cancer (EOC). Our results have shown that Circ-NOLC1 expression was higher in EOC tissues than in normal tissues, and was positively associated with FIGO stage, differentiation. Among ovarian cancer cell lines, circ-NOLC1 expression was the highest in A2780, and lowest in CAOV3. Overexpression of circ-NOLC1 in CAOV3 cells increased cell proliferation, migration, and invasion ability, whereas silencing of circ-NOLC1 in A2780 cells had the opposite effect: however, neither circ-NOLC1 downregulation nor overexpression influenced NOLC1 mRNA expression. In nude mice with subcutaneous tumors, circ-NOLC1 downregulation decreased tumor growth. Bioinformatic analysis and RNA-binding protein immunoprecipitation showed that circ-NOLC1 could bind to ESRP1. In addition, the overexpression of circ-NOLC1 significantly increased ESRP1, RhoA, and CDK1 protein and mRNA expression level; circ-NOLC1 downregulation had the opposite effects. The tumor-promoting effect of circ-NOLC1 was inhibited by knockdown of ESRP1, CDK1, or RhoA expression in circ-NOLC1-overexpressing cells, which might act by modulating RhoA and CDK1 expression. In conclusion, our study demonstrated that Circ-NOLC1 might promote EOC tumorigenesis and development by binding ESRP1 and modulating CDK1 and RhoA expression.
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BACKGROUND: Circular RNAs are key regulators in human cancers, however, there is a lack of studies on circRNAs' specific functions in ovarian cancer. METHODS: Our study used qRT-PCR to detect the differentially expressed circRNAs between normal ovaries and ovarian cancer tissues. Cell function experiments were performed to verify the role of overexpression and silence of circWHSC1, including MTT assay, cell apoptosis assay, wound healing and Matrigel-coated Transwell assay. In vivo tumorigenesis model was constructed by subcutaneous injection in nude mice. Bioinformatics analysis predicted the possible binding sites of circWHSC1 with miRNAs, and confirmed with dual-luciferase reporter assay and RNA pull-down assay. The exosomes were extracted with ultracentrifugation. HE staining was also used to detect morphology of nude mice peritoneum. RESULTS: We found that circWHSC1 was up-regulated in ovarian cancer tissues, and circWHSC1 expression was higher in moderate & poor differentiation ovarian cancer tissues than in well differentiation ovarian cancer tissues. Overexpression of circWHSC1 increased cell proliferation, migration and invasion, and inhibited cell apoptosis. Silence of circWHSC1 exerted the opposite effects. Additionally, circWHSC1 could sponge miR-145 and miR-1182 and up-regulate the expression of downstream targets MUC1 and hTERT. Exosomal circWHSC1 can be transferred to peritoneal mesothelial cells and promotes peritoneal dissemination. CONCLUSIONS: Our study demonstrates the highly expressed circWHSC1 in ovarian cancer promotes tumorigenesis by sponging miR-145 and miR-1182, and its exosome forms induce tumor metastasis through acting on peritoneal mesothelium.
Assuntos
Carcinoma Epitelial do Ovário/patologia , MicroRNAs/genética , Mucina-1/genética , Neoplasias Ovarianas/patologia , RNA Circular/genética , Telomerase/genética , Animais , Carcinoma Epitelial do Ovário/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Nus , Transplante de Neoplasias , Neoplasias Ovarianas/genéticaRESUMO
Circular RNAs are known to participate in tumorigenesis through a variety of pathways, and as such, have potential to serve as molecular markers in tumor diagnosis and treatment. Here, using quantitative reverse transcription (qRT)-PCR, we showed that circ-CSPP1 is highly expressed in ovarian cancer (OC) tissues. Particularly, we detected circ-CSPP1 expression in three OC cell lines; of which, OVCAR3 and A2780 demonstrated higher levels of circ-CSPP1 expression, and CAOV3 showed lower circ-CSPP1 expression level. Subsequent silencing of circ-CSPP1 in OVCAR3 and A2780 cell lines revealed decreased cell growth, migration and invasion, while overexpression of circ-CSPP1 caused opposite results We also found that miR-1236-3p is a target of circ-CSPP1. Circ-CSPP1 silencing increased the expression of miR-1236-3p, and circ-CSPP1 overexpression decreased miR-1236-3p expression. MiR-1236-3p reportedly plays a tumor-suppressor role in OC by targeting zinc finger E-box binding homeobox 1 (ZEB1). In agreement with this, we showed that silencing circ-CSPP1 significantly decreased ZEB1 expression at both RNA and protein levels, and epithelial-mesenchymal transition (EMT) related markers (E-cadherin and N-cadherin) varied with ZEB1 expression. Circ-CSPP1 silencing also caused decreased expression of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor A (VEGFA), both of which are related to tumorigenesis. Overexpression of circ-CSPP1 had opposite effects. In addition, we indicated that the tumor-promoting effect was inhibited after we transfected miR-1236-3p into circ-CSPP1 overexpressing OC cells. Altogether, our findings suggest that by acting as a miR-1236-3p sponge, circ-CSPP1 impairs the inhibitory effect of miR-1236-3p on ZEB1, which subsequently promotes EMT and OC development.
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Proteínas de Ciclo Celular/genética , Movimento Celular/genética , Proliferação de Células/genética , MicroRNAs/genética , Proteínas Associadas aos Microtúbulos/genética , Neoplasias Ovarianas/genética , RNA/genética , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células HEK293 , Humanos , Metaloproteinase 2 da Matriz/genética , Neoplasias Ovarianas/patologia , RNA Circular , Fator A de Crescimento do Endotélio Vascular/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genéticaRESUMO
AIM: To investigate the effect of 7-(4-methoxyphenyl)-5, 8a-diphenyl-1, 2, 3, 7, 8, 8a-hexahydroimidazo[1, 2-a]pyridine (TIP-6) on cell proliferation in human hepatoma cell line HepG2 and human normal hepatocyte cell line L02. METHODS: Typan blue assay was used to check the effect of TIP-6 on cell proliferation. The changes of cell morphology were observed by the phase contrast microscope. Flow cytometry (FCM) was used to check cell cycle. Autophagy and autophagic cell death were detected after acridine orange (AO) staining under fluorescent microscopy. Apoptosis was analyzed by Annexin V/7-AAD, DAPI staining and DNA ladder. NF-kappaB expression was detected with cellular immunochemistry. RESULTS: Cell proliferation inhibiting effect was appeared when treated with TIP-6 from 60 mumol/L to 200 mumol/L, which was correlated with treated concentrations and time. The proliferation rates were just 12.10% and 18.75% (vs control) under 200 mumol/L 72 h in HepG2 and L02 respectively. Vacuolization were found more and more frequently with the increasing of TIP-6 concentrations and treated time prolonged. FCM results indicated that cells were blocked in G2/M phase, and more sensitive were found in HepG2 than L02. AO staining results indicated that the phenomenon of autophagy and autophagic cell death were occurred and appeared more potent with more TIP-6 and longer time treated. No apoptosis markers were found with Annexin V/7-AAD and DAPI staining, and no DNA ladders were found either, these indicated that TIP-6 didn't induce apoptosis in these cells. NF-kappaB was found increased after treated with TIP-6, and the autophagic vacuole became more and more with the increasing of NF-kappaB protein, but the proliferation rates decreased at the same time. CONCLUSION: TIP-6 inhibited cell proliferation and induced autophagy and autophagic cell death in HepG2 and L02 cells. NF-kappaB activation may be involved in these effects.
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Autofagia/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Hepatócitos/citologia , Piridinas/farmacologia , Animais , Contagem de Células , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Hepatócitos/efeitos dos fármacos , Humanos , Fatores de TempoRESUMO
PURPOSE: To investigate the relationship between condylar marrow signal abnormalities and joint pain. METHODS: Oblique sagittal T1 and T2 weighted MR imaging at closed mouth was obtained from 88 joints of 44 patients who complained of unilateral TMJ pain. The condylar marrow signal of pain-free side served as self-control. All patients rated their pain levels by a visual analogue scale (VAS). RESULTS: Of 44 painful joints, 11(25% joints showed condylar marrow signal abnormalities, all of which were edema pattern. While there had condylar marrow signal abnormalities only in 2 (4.5%) of 44 pain-free TMJs. There was significant correlation between joint pain and condylar marrow signal abnormalities (P<0.01). The VAS score of patients with and without condylar marrow signal abnormalities was respectively 39.5+/-27.5 and 42.6+/-21.9, There was no correlation between them (P=0.696). CONCLUSION: Temporomandibular joint pain is closely correlated with condylar marrow signal abnormalities, but the pain degree has no association with it.
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Artralgia/diagnóstico , Doenças da Medula Óssea/patologia , Côndilo Mandibular/patologia , Transtornos da Articulação Temporomandibular/diagnóstico , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
In order to determine the appraisal of ABO blood group accurately and ensure the safety of blood transfusion, an investigation was made on the influence of complement activated by antibody in appraising ABO blood group by using hemoagglutination test and direct antiglobulin test. Two samples of ABO blood group were collected from two donors. The results showed that the obverse and reverse patterns did not accord each other in two samples of ABO blood group, and their blood samples were both positive for anti-C(3) and were both negative for anti-IgG. It is concluded that the inconsistency of the obverse and reverse patterns in two samples of ABO blood group were proved to be caused by the complements activated by the antibody against IgM. Blood group O was finally determined for the two samples, and the influences of IgM antibody and complement on ABO blood group were excluded when the test proceeded. This method will be useful to determine ABO blood group accurately.