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Recently, an increasing number of studies have reported that dysregulation of circular RNA (circRNA) expression plays critical roles in the progression of several cancers, including colorectal cancer (CRC). However, the detailed molecular mechanisms of circRNAs involvement in CRC remain largely unknown. Here, we confirmed that the level of circEGFR was significantly increased in CRC tissues compared to matched adjacent non-tumor tissues, and a high level of circEGFR was correlated with poor clinicopathological characteristics and poor prognosis in patients with CRC. Moreover, increased circEGFR expression promoted CRC cell proliferation, migration, and invasion in vitro. Mechanistically, circEGFR acted as a ceRNA for miR-106a-5p to relieve the repressive effect of miR-106a-5p on DDX5 mRNA. Moreover, circEGFR enhanced DDX5 expression, thereby upregulating p-AKT levels. Together, these findings showed that circEGFR promoted CRC cell proliferation, migration, and invasion through the miR-106a-5p/DDX5/AKT axis, and may serve as a promising diagnostic marker and therapeutic target for CRC patients.
Subject(s)
Humans , Colorectal Neoplasms/genetics , MicroRNAs/genetics , Gene Expression Regulation, Neoplastic , Cell Movement/genetics , Cell Line, Tumor , Cell Proliferation/genetics , DEAD-box RNA Helicases , RNA, CircularABSTRACT
AIM: To investigate the regulation function of miR-106a on the proliferation of human ovarian granulosa cells, and to explore its possible target.METHODS: The expression of miR-106a in granulosa cells was regulated by cell transfection, and its expression level was detected by RT-PCR. The MTT assay was used to detect the cell proliferation activities of cells. Bioinformatics methods were used to predicted the possible target genes of miR-106a, which were verified them by double-luciferase assay. The expression of target protein was detected by Western blot. RESULTS:The expression of miR-106a in KGN cells was significantly higher than that of normal ovarian epithelial cell (IOSE80), the difference was statistically significant (P<0.05). The proliferation activity of KGN cells was significantly decreased after inhibiting the expression of miR-106a (P<0.05). The results of dual luciferase assay showed that miR-106a could directly target TIMP-2 gene. Western blot results showed that the expression level of TIMP-2 protein was significantly decreased after overexpression of miR-106a (P<0.05). CONCLUSION: miR-106a can promote the proliferation of KGN cell; The mechanism is related to the targeted reduction of TIMP-2 expression level.
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Osteoarthritis (OA), a type of joint diseases, could result in breakdown of joint cartilage and underlying bone. Accumulating evidences suggested that long non-coding RNAs play important roles in OA progression. However, the underlyingmechanism of H19 in OA is still not fully explored. The expression levels of H19 and miR-106a-5p in OA samples frompatients or cultured chondrocytes were examined by quantitative real time polymerase chain reaction. Cell proliferation andapoptosis were analysed by MTT assay and flow cytometry, respectively. Western blotting was employed to detect theexpression levels of PCNA, CyclinD1, Caspase 3 and Cleaved Caspase 3. StarBase database, luciferase assay and RNAimmunoprecipitation were introduced to confirm the relationship between H19 and miR-106a-5p. The correlation of H19and miR-106a-5p was analysed by Spearman rank analysis. H19 expression was upregulated, while miR-106a-5p level wasdownregulated in OA samples and IL-1b-treated chondrocytes. H19 overexpression inhibited the proliferation and inducedapoptosis in IL-1b-treated chondrocytes, while H19 knockdown induced the opposite effect. Luciferase and RIP assaydemonstrated that miR-106a-5p was a direct target of H19. miR-106a-5p overexpression led to proliferation promotion andapoptosis inhibition in chondrocytes treated by IL-1b and it reversed the effect of H19 addition. We conclude that H19could regulate proliferation and apoptosis of chondrocytes treated by IL-1b in OA via sponging miR-106a-5p
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Objective To investigate the role of microRNA-106a and microRNA-106b (miR-106a/b) in diagnosis and prognosis of hepatocellular carcinoma (HCC).Methods In this study,108 HCC patients and 54 age-and sex-matched healthy controls were enrolled.Blood samples were collected from each participant,and total RNA was extracted from the plasma.We determined miR-106a/b expression levels using quantitative reverse transcription polymerase chain reaction (qRT-PCR).Results The miR-106a/b expression levels in HCC patients were elevated compared with the healthy controls (P＜ 0.001).The ROC curve analysis showed that miR-106a/b expression levels could be used to predict the risk of HCC,with AUC values of 0.670 (95％ CI:0.573-0.768) and 0.684 (95％ CI:0.593-0.776),respectively.The miR-106a expression level in HCC patients correlated positively with hepatitis B surface antigen (HBsAg) presence (P =0.028),differentiation (P =0.025),tumor size (P =0.002),lymph node metastasis (P =0.028),and TNM stage (P =0.037).The miR-106b expression level correlated positively with HBsAg presence (P =0.003),alpha-fetoprotein (AFP) level (P =0.031),and tumor size (P =0.005).To further investigate the correlation of miR-106a/b expression levels with overall survival (OS),Kaplan-Meier curves were plotted.The results showed that HCC patients with high miR-106a expression displayed shorter OS (P =0.013).In addition,univariate and multivariate Cox proportional hazards regression showed that miR-106a was an independent risk factor for HCC prognosis.Conclusion Circulating miR-106a/b expression levels could be used as diagnostic biomarkers for HCC,and a high circulating miR-106a expression level is an independent risk factor for poor prognosis of HCC patients.
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OBJECTIVE@#To study the inhibition effect of miR-106a inhibitor on tumor growth of ovarian cancer xenografts mice.@*METHODS@#BALB/c mice were selected as experimental animals, ovarian cancer SKOV-3 cells transfected with miR-106a inhibitor and its negative control were inoculated subcutaneously, intratumoral injection of miR-106a inhibitor and its negative control were continued after tumor formation, and they were enrolled as treatment group and model group, respectively. Tumor volume and weight as well as Ki-67 and programmed cell death 4 (PDCD4) expression were determined; miR-106a inhibitor and its negative control as well as miR-106a mimic and its negative control were transfected into SKOV-3 cells, and expression of PDCD4 in cells was determined.@*RESULTS@#Tumor tissue volume and weight as well as mRNA expression and protein expression of Ki-67 in treatment group were significantly lower than those in the model group while mRNA expression and protein expression of PDCD4 were significantly higher than those in the model group; transfection of miR-106a mimic could decrease mRNA expression and protein expression of PDCD4 in SKOV-3 cells, and transfection of miR-106a inhibitor could increase mRNA expression and protein expression of PDCD4 in SKOV-3 cells.@*CONCLUSIONS@#Transfection of miR-106a inhibitor can inhibit the growth of tumor in ovarian cancer xenografts mice through increasing the expression of PDCD4.
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Objective To study the inhibition effect of miR-106a inhibitor on tumor growth of ovarian cancer xenografts mice. Methods BALB/c mice were selected as experimental animals, ovarian cancer SKOV-3 cells transfected with miR-106a inhibitor and its negative control were inoculated subcutaneously, intratumoral injection of miR-106a inhibitor and its negative control were continued after tumor formation, and they were enrolled as treatment group and model group, respectively. Tumor volume and weight as well as Ki-67 and programmed cell death 4 (PDCD4) expression were determined; miR-106a inhibitor and its negative control as well as miR-106a mimic and its negative control were transfected into SKOV-3 cells, and expression of PDCD4 in cells was determined. Results Tumor tissue volume and weight as well as mRNA expression and protein expression of Ki-67 in treatment group were significantly lower than those in the model group while mRNA expression and protein expression of PDCD4 were significantly higher than those in the model group; transfection of miR-106a mimic could decrease mRNA expression and protein expression of PDCD4 in SKOV-3 cells, and transfection of miR-106a inhibitor could increase mRNA expression and protein expression of PDCD4 in SKOV-3 cells. Conclusions Transfection of miR-106a inhibitor can inhibit the growth of tumor in ovarian cancer xenografts mice through increasing the expression of PDCD4.
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Purpose To investigate the comparison of miR-106a in fresh and paraffin-embedded tissues and its expression in precan-cerous 1esions of gastric cancer. Methods Human gastric cancer tissues inc1uding 30 coup1es of fresh and 40 coup1es of paraffin-em-bedded samp1es were co11ected,quantitative rea1-time PCR was used to detect the expression of miR-106a in these two samp1es. Anoth-er paraffin-embedded samp1es inc1uding 20 cases of precancerous 1esions and 40 cases of gastric adenocarcinoma were a1so co11ected,in situ hybridization was used to assess the expression of miR-106a in these stages. Results The re1ative expression of miR-106a in fresh tissues was 3. 25 ± 1. 99,in paraffin-embedded tissues was 3. 18 ± 2. 14,indicating that the expression of miR-106a in these two sam-p1es has no statistica1 difference(P>0. 05),corre1ation ana1ysis showed that there was a significant corre1ation of miR-106a expression in these two samp1es(rs =0. 998,P<0. 001). The expression of miR-106a was detected in the stage of precancerous 1esions with the positive rate was 70%. The positive signa1s were 1ocated in dysp1astic epithe1ia1 ce11s and appeared as dark b1ue fine granu1es. The positive rate of miR-106a in gastric cancer tissues was 87. 5% and the frequency and extent increased and enhanced compared with pre-cancerous 1esions. Conclusion miR-106a has significant corre1ation in gastric cancer fresh tissues and paraffin-embedded tissues. Detection of miR-106a with paraffin tissues and its ear1y changes in prema1ignant 1esions can provide va1uab1e information for the ear1y diagnosis of gastric cancer.
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Objective To detect the circulating miR-106a levels in serum before and after surgery in patients with renal clear cell carcinoma,and to explore its relationship with clinical-pathological parameters.Methods 30 serum samples from patients with renal clear cell carcinoma were collected before and after surgery during February 2013 to July 2014.This study included 30 normal controls.All serum miR-106a levels were detected using the real-time PCR.Results The serum miR-l06a levels in patients with renal clear cell carcinoma pre-operatively wcre significantly greater than normal controls (Z =-4.251,P =0.0001).The serum miR-106a levels in patients post-operatively had no significant differences compared to normal controls (Z =-0.244,P =0.807).The serum miR-106a levels in post-operative samples were significantly lower than the pre-operative samples (Z =-4.229,P =0.0001).Serum miR-106a levels and other clinical-pathological parameters had no correlation in patients with renal clear cell carcinoma(tumor size:Z =-0.775,P =0.439;Fuhrman grade:Z =-1.694,P =0.090).The receiver operating characteristic curve was used to distinguish pre-operative samples and normal controls,its AUC was 0.819 (95％ CI:0.710-0.929,P =0.0001) with 86.7％ sensitivity and 70.0％ specificity.Conclusions The serum miR-106a levels in patients with renal clear cell carcinoma pre-operatively were significantly greater than post-operatively with no correlation in tumor size and Fuhrman grade.The outcome suggested that serum miR-106a can be regarded as a potential molecular marker in renal clear cell carcinoma.
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Objective To detect the correlations of miR -106 a expression with clinical features of pa-tients with colon cancer ,and to explore the significance of miR -106 a as a prognostic factor .Methods One hun-dred and five patients with primary colon cancer were retrospectively enrolled in this study including their clinical information and slices of FFPE.miR-106a expression was detected by qRT -PCR,and analyzed the correlation between the level of miR -106a and clinical features and survival .Results The level of miR -106a in tumor tissue was higher than adjacent normal tissue (1.142 vs.0.685,P<0.001).miR-106a was correlated with TNM stage and lymphnode metastasis .The higher miR -106a expression,the poorer survival patients were .The hazard risk was increased 3.390 folds(95%CI for HR:1.028 ~11.178)when compared high expression group with the low.Conclusion The aberrant expression of miR -106a may be associated with colon cancer .It will po-tentially be a therapeutic target and prognostic factors .