• Title, Summary, Keyword: miR-20a

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Aberrant Expression of miR-20a and miR-203 in Cervical Cancer

  • Zhao, Shan;Yao, De-Sheng;Chen, Jun-Ying;Ding, Nan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2289-2293
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    • 2013
  • MicroRNAs (miRNAs) are small, non-coding RNAs that are critical regulators of various diseases. MicroRNA-20a (miR-20a) and microRNA-203 (miR-203) have previously shown significant alteration in a range of cancers. In this study, the expression levels of miR-20a and miR-203 in 100 cervical cancer tissues were detected by qRT-PCR and compared to patient matched-nontumor cervical tissues. Correlations between expression level and clinicopathologic characteristics of cervical cancer were also analyzed. Finally, we studied the effect of miR-20a and miR-203 on cell proliferation in cervical cancer cell lines by MTT. We found that the expression level of miR-20a (P<0.001) was significantly higher in cervical cancer patients than in healthy controls, while that of miR-203 (P<0.001) was lower. Aberrant expression of miR-20a was correlated with lymph node metastasis (LNM), histological grade and tumor diameter, but down-regulated miR-203 was correlated with LNM only. Furthermore, we found that over-expression of miR-203 decreased cell proliferation, while reduction of miR-20a also prevented tumor progression. Our results support the involvement of miR-20a and miR-203 in cervical tumorigenesis. We propose that miRNAs might be used as therapeutic agents for cervical cancer.

Differential Distribution of miR-20a and miR-20b may Underly Metastatic Heterogeneity of Breast Cancers

  • Li, Jian-Yi;Zhang, Yang;Zhang, Wen-Hai;Jia, Shi;Kang, Ye;Zhu, Xiao-Yu
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.1901-1906
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    • 2012
  • Background: The discovery that microRNA (miRNA) regulates metastasis provide a principal molecular basis for tumor heterogeneity. A characteristic of solid tumors is their heterogenous distribution of blood vessels, with significant hypoxia occurring in regions (centers of tumor) of low blood flow. It is necessary to discover the mechanism of breast cancer metastasis in relation to the fact that there is a differential distribution of crucial microRNA in tumors from centers to edges. Methods: Breast tissues from 48 patients (32 patients with breast cancer) were classified into the high invasive and metastatic group (HIMG), low invasive and metastatic group (LIMG), and normal group. Samples were collected from both the centers and edges of all tumors. The first six specimens were detected by microRNA array, and the second ten specimens were detected by real-time qRT-PCR and Western blot analyses. Correlation analysis was performed between the miRNAs and target proteins. Results: The relative content of miR-20a and miR-20b was lower in the center of the tumor than at the edge in the LIMG, lower at the edge of the tumor than in the center in the HIMG, and lower in breast cancer tissues than in normal tissues. VEGF-A and HIF-1alpha mRNA levels were higher in the HIMG than in the LIMG, and levels were higher in both groups than in the normal group; there was no difference in mRNA levels between the edge and center of the tumor. VEGF-A and HIF-1alpha protein levels were higher in the HIMG than in the LIMG, and protein levels in both groups were higher than in the normal group; there was a significant difference in protein expression between the edge and center of the tumor. Correlation analysis showed that the key miRNAs (miR-20a and miR-20b) negatively correlated with the target proteins (VEGF-A and HIF-1alpha). Conclusions: Our data suggest that miR-20a and miR-20b are differentially distributed in breast cancer, while VEGF-A and HIF-1alpha mRNA had coincident distributions, and VEGF-A and HIF-1alpha proteins had uneven and opposing distributions to the miRNAs. It appears that one of the most important facets underlying metastatic heterogeneity is the differential distribution of miR-20a and miR-20b and their regulation of target proteins.

Expression of MicroRNA-221 in Korean Patients with Multiple Myeloma (한국인의 다발성골수종 환자에서 MicroRNA-221의 발현)

  • Choi, Woo-Soon
    • Korean Journal of Clinical Laboratory Science
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    • v.50 no.2
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    • pp.197-204
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    • 2018
  • Multiple myeloma (MM) is the leading cause of death among hematologic neoplasms. Recently, microRNA has been reported to be useful in the diagnosis of multiple myeloma. This study examined whether miR-221 could be used as a diagnostic marker for multiple myeloma. The study was performed on 20 patients with multiple myeloma without any other hematological diseases. MicroRNA extraction was performed using formalin-fixed paraffin-embedded (FFPE) tissues obtained from the bone marrow of patients with multiple myeloma. miR-15a, miR-16, miR-21, miR-181a, and miR-221 were selected as the microRNA target genes for multiple myeloma. The significance of microRNA was based on a fold change of <1.5. To quantify the fold changes, data normalized to the human gene, SNORD43, were used as the values of the patient group. Fold change values greater than 1.5 were defined as "overexpression", whereas values less than -1.5 were defined as "underexpression". Of note, 65.0% (13/20) of samples showed significant "overexpression" in the levels of miR-221 expression and plasma cells with a group of more and less than 30% in MM patients did not show any significance of plasma cell (P<0.05). The results of other studies showing a correlation between the expression of miR-221 and MM in Caucasians were confirmed. These results suggest that miR-221 may be a useful indicator for diagnosing patients with MM. In conclusion, miR-221 is useful in the diagnosis and determining the prognosis of multiple myeloma in Koreans.

microRNA Expression Profile in Patients with Stage II Colorectal Cancer: A Turkish Referral Center Study

  • Tanoglu, Alpaslan;Balta, Ahmet Ziya;Berber, Ufuk;Ozdemir, Yavuz;Emirzeoglu, Levent;Sayilir, Abdurrahim;Sucullu, Ilker
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1851-1855
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    • 2015
  • Background: There are increasing data about microRNAs (miRNA) in the literature, providing abundant evidence that they play important roles in pathogenesis and development of colorectal cancer. In this study, we aimed to investigate the miRNA expression profiles in surgically resected specimens of patients with recurrent and non-recurrent colorectal cancer. Materials and Methods: The study population included 40 patients with stage II colorectal cancer (20 patients with recurrent tumors, and 20 sex and age matched patients without recurrence), who underwent curative colectomy between 2004 and 2011 without adjuvant therapy. Expression of 16 miRNAs (miRNA-9, 21, 30d, 31, 106a, 127, 133a, 133b, 135b, 143, 145, 155, 182, 200a, 200c, 362) was verified by quantitative real-time polymerase chain reaction (qRT-PCR) in all resected colon cancer tissue samples and in corresponding normal colonic tissues. Data analyses were carried out using SPSS 15 software. Values were statistically significantly changed in 40 cancer tissues when compared to the corresponding 40 normal colonic tissues (p<0.001). MiR-30d, miR-133a, miR-143, miR-145 and miR-362 expression was statistically significantly downregulated in 40 resected colorectal cancer tissue samples (p<0.001). When we compared subgroups, miRNA expression profiles of 20 recurrent cancer tissues were similar to all 40 cancer tissues. However in 20 non-recurrent cancer tissues, miR-133a expression was not significantly downregulated, moreover miR-133b expression was significantly upregulated (p<0.05). Conclusions: Our study revealed dysregulation of expression of ten miRNAs in Turkish colon cancer patients. These miRNAs may be used as potential biomarkers for early detection, screening and surveillance of colorectal cancer, with functional effects on tumor cell behavior.

miR-200a Overexpression in Advanced Ovarian Carcinomas as a Prognostic Indicator

  • Zhu, Cheng-Liang;Gao, Guo-Sheng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.20
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    • pp.8595-8601
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    • 2014
  • Background: miR-200a expression is frequently altered in numerous cancers. The aim of the present study was to determine the role of microRNA-200a in advanced ovarian carcinomas. Materials and Methods: We measured miR-200a expression in 72 matched normal ovarian tissues and advanced ovarian carcinomas, and also two ovarian carcinoma cell lines (SKOV3 and SKOV3.ip1 - the latter being more invasive and metastatic than the parental SKOV3) by stem-loop real-time RT-PCR based on TaqMan microRNA assay using U6 as a reference. Levels of miR-200a expression were compared by disease stage, tumor grade, histology, and lymph node involvement. To evaluate the role of microRNA-200a, cell proliferation and invasion of SKOV-3 and SKOV-3.ip1 were analyzed with miR-200a inhibitor/mimic transfected cells. Results: Of 72 paired samples, 65 cancer tissues overexpressed microRNA-200a greater than two fold in comparison with matched normal epithelium. Specifically, patients with lymph node metastasis showed significant elevation. The level correlated with clinicopathological features, including high tumor grade, late disease stage, most notably with lymph node metastasis, but not with tumor histology. In addition, SKOV-3.ip1 cells also overexpressed miR-200a compared with SKOV-3, and miR-200a inhibitor transfected SKOV-3.ip1 cells showed significant reduction in cellular proliferation and invasion, while a miR-200a mimic stimulated the opposite behavior. Conclusions: We provide definitive evidence that miR-200a is up-regulated in a significant proportion of advanced ovarian carcinomas, and that elevated miR-200a expression facilitates tumor progression. Our findings support the notion that miR-200a is an onco-microRNA for ovarian cancer, and elevation is a useful potential diagnostic indicator. This study also provides a solid basis for further functional analysis of miR-200a in advanced ovarian cancer.

Relationship between porcine miR-20a and its putative target low-density lipoprotein receptor based on dual luciferase reporter gene assays

  • Ding, Yueyun;Zhu, Shujiao;Wu, Chaodong;Qian, Li;Li, DengTao;Wang, Li;Wan, Yuanlang;Zhang, Wei;Yang, Min;Ding, Jian;Wu, Xudong;Zhang, Xiaodong;Gao, Yafei;Yin, Zongjun
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.7
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    • pp.922-929
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    • 2019
  • Objective: Mutations in low-density lipoprotein receptor (LDLR), which encodes a critical protein for cholesterol homeostasis and lipid metabolism in mammals, are involved in cardiometabolic diseases, such as familial hypercholesterolemia in pigs. Whereas microRNAs (miRNAs) can control LDLR regulation, their involvement in circulating cholesterol and lipid levels with respect to cardiometabolic diseases in pigs is unclear. We aimed to identify and analyze LDLR as a potential target gene of SSC-miR-20a. Methods: Bioinformatic analysis predicted that porcine LDLR is a target of SSC-miR-20a. Wild-type and mutant LDLR 3'-untranslated region (UTR) fragments were generated by polymerase chain reaction (PCR) and cloned into the pGL3-Control vector to construct pGL3 Control LDLR wild-3'-UTR and pGL3 Control LDLR mutant-3'-UTR recombinant plasmids, respectively. An miR-20a expression plasmid was constructed by inserting the porcine premiR-20a-coding sequence between the HindIII and BamHI sites in pMR-mCherry, and constructs were confirmed by sequencing. HEK293T cells were co-transfected with the miR-20a expression or pMR-mCherry control plasmids and constructs harboring the corresponding 3'-UTR, and relative luciferase activity was determined. The relative expression levels of miR-20a and LDLR mRNA and their correlation in terms of expression levels in porcine liver tissue were analyzed using reverse-transcription quantitative PCR. Results: Gel electrophoresis and sequencing showed that target gene fragments were successfully cloned, and the three recombinant vectors were successfully constructed. Compared to pMR-mCherry, the miR-20a expression vector significantly inhibited wild-type LDLR3'-UTR-driven (p<0.01), but not mutant LDLR-3'-UTR-driven (p>0.05), luciferase reporter activity. Further, miR-20a and LDLR were expressed at relatively high levels in porcine liver tissues. Pearson correlation analysis revealed that porcine liver miR-20a and LDLR levels were significantly negatively correlated (r = -0.656, p<0.05). Conclusion: LDLR is a potential target of miR-20a, which might directly bind the LDLR 3'-UTR to post-transcriptionally inhibit expression. These results have implications in understanding the pathogenesis and progression of porcine cardiovascular diseases.

MicroRNA-222 Expression as a Predictive Marker for Tumor Progression in Hormone Receptor-Positive Breast Cancer

  • Han, Song-Hee;Kim, Hyun Jeong;Gwak, Jae Moon;Kim, Mimi;Chung, Yul Ri;Park, So Yeon
    • Journal of Breast Cancer
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    • v.20 no.1
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    • pp.35-44
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    • 2017
  • Purpose: The microRNA-221/222 (miR-221/222) gene cluster has been reported to be associated with the promotion of epithelial-mesenchymal transition (EMT), downregulation of estrogen receptor-${\alpha}$, and tamoxifen resistance in breast cancer. We studied the expression of miR-222 in human breast cancer samples to analyze its relationship with clinicopathologic features of the tumor, including estrogen receptor status, expression of EMT markers, and clinical outcomes. Methods: Quantitative real-time polymerase chain reaction was performed to detect the expression of miR-222 in 197 invasive breast cancers. Expression of EMT markers (vimentin, smooth muscle actin, osteonectin, N-cadherin, and E-cadherin) was evaluated using immunohistochemistry. Results: High miR-222 levels were associated with high T stage, high histologic grade, high Ki-67 proliferation index, and HER2 gene amplification. Its expression was significantly higher in the luminal B and human epidermal growth factor receptor 2-positive (HER2+) subtypes than in the luminal A and triple-negative subtypes. In the hormone receptor-positive subgroup, there was a significant negative correlation between miR-222 and estrogen receptor expression, and miR-222 expression was associated with EMT marker expression. In the group as a whole, high miR-222 expression was not associated with clinical outcome. However, subgroup analyses by hormone receptor status revealed that high miR-222 expression was a poor prognostic factor in the hormone receptor-positive subgroup, but not in the hormone receptor-negative subgroup. Conclusion: This study showed that miR-222 is associated with down-regulation of the estrogen receptor, EMT, and tumor progression in hormone receptor-positive breast cancer, indicating that miR-222 might be associated with endocrine therapy resistance and poor clinical outcome in hormone receptor-positive breast cancer.

Association of miR-193b Down-regulation and miR-196a up-Regulation with Clinicopathological Features and Prognosis in Gastric Cancer

  • Mu, Yong-Ping;Tang, Song;Sun, Wen-Jie;Gao, Wei-Min;Wang, Mao;Su, Xiu-Lan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.20
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    • pp.8893-8900
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    • 2014
  • Dysregulated expression of microRNAs (miRNAs) has been shown to be closely associated with tumor development, progression, and carcinogenesis. However, their clinical implications for gastric cancer remain elusive. To investigate the hypothesis that genome-wide alternations of miRNAs differentiate gastric cancer tissues from those matched adjacent non-tumor tissues (ANTTs), miRNA arrays were employed to examine miRNA expression profiles for the 5-pair discovery stage, and the quantitative real-time polymerase chain reaction (qRTPCR) was applied to validate candidate miRNAs for 48-pair validation stage. Furthermore, the relationship between altered miRNA and clinicopathological features and prognosis of gastric cancer was explored. Among a total of 1,146 miRNAs analyzed, 16 miRNAs were found to be significantly different expressed in tissues from gastric cancer compared to ANTTs (p<0.05). qRT-PCR further confirmed the variation in expression of miR-193b and miR-196a in the validation stage. Down-expression of miR-193b was significantly correlated with Lauren type, differentiation, UICC stage, invasion, and metastasis of gastric cancer (p<0.05), while over-expression of miR-196a was significantly associated with poor differentiation (p=0.022). Moreover, binary logistic regression analysis demonstrated that the UICC stage was a significant risk factor for down-expression of miR-193b (adjusted OR=8.69; 95%CI=1.06-56.91; p=0.043). Additionally, Kaplan-Meier survival curves indicated that patients with a high fold-change of down-regulated miR-193b had a significantly shorter survival time (n=19; median survival=29 months) compared to patients with a low fold-change of down-regulated miR-193b (n=29; median survival=54 months) (p=0.001). Overall survival time of patients with a low fold-change of up-regulated miR-196a (n=27; median survival=52 months) was significantly longer than that of patients with a high fold-change of up-regulated miR-196a (n=21; median survival=46 months) (p=0.003). Hence, miR-193b and miR-196a may be applied as novel and promising prognostic markers in gastric cancer.

Circulating Cell-free miRNA Expression and its Association with Clinicopathologic Features in Inflammatory and Non-Inflammatory Breast Cancer

  • Hamdi, K;Blancato, J;Goerlitz, D;Islam, MD;Neili, B;Abidi, A;Gat, A;Ayed, F Ben;Chivi, S;Loffredo, CA;Jillson, I;Elgaaied, A Benammar;Marrakchi, R
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.4
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    • pp.1801-1810
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    • 2016
  • Recent discovery showing the presence of microRNAs (miRNAs) in the circulation sparked interest in their use as potential biomarkers. Our previous studies showed the diagnostic potential of miR-451 as a serological marker for inflammatory breast cancer (IBC), miR-337-5p and miR-30b for non-inflammatory breast cancer (non-IBC). The aim of this study is to investigate the prognostic values of circulating miRNAs by comparing the amounts of 12 circulating miRNAs in the serum of IBC and non-IBC from Tunisian breast cancer patients, and by determinating whether correlated pairs of miRNAs could provide useful information in the diagnosis of IBC and non-IBC patients. TaqMan qPCR was performed to detect circulating expression of miRNAs in serum of 20 IBC, 20 non-IBC and 20 healthy controls. Nonparametric rank Spearman rho correlation coefficient was used to examine the prognostic value of miRNAs and to assess the correlation profile between miRNAs expression. Further, a large number of miRNAs were highly correlated (rho>0.5) in both patients groups and controls. Also, the correlations profiles were different between IBC, non-IBC and healthy controls indicating important changes in molecular pathways in cancer cells. Our results showed that miR-335 was significantly overexpressed in premenopausal non-IBC patients; miR-24 was significantly overexpressed in non-IBC postmenopausal patients. Patients with previous parity had higher serum of miR-342-5p levels than those without. Furthermore, patients with HER2+ IBC present lower serum levels of miR-15a than patients with HER2-disease. Together, these results underline the potential of miRNAs to function as diagnostic and prognostic markers for IBC and non-IBC, with links to the menopausal state, Her2 status and parity.

Expressions of MicroRNA-150 and MicroRNA-424 Targeted to C-reactive Protein in Trophoblast Cell Line (영양막세포에서의 C-reactive protein 조절 microRNA-150과 microRNA-424 발현 분석)

  • Kim, Hee Sung
    • The Journal of the Korea Contents Association
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    • v.19 no.11
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    • pp.375-382
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    • 2019
  • Abnormalities of trophoblast due to early inflammation in pregnancy increase the expression of CRP and affect maternal-fetal interactions, leading to preterm birth and preeclampsia. However, biomarkers related to the regulation of CRP expression have not been found. In this study, miRNA associated with increased expression of CRP was identified and their expression was analyzed to reveal biomarkers involved in the regulation mechanism of trophoblast inflammation through miRNAs. miRNAs that were predicted to regulate CRP gene expression in miRNA databases (mirna, TargetScan, MicroCosm) were screened and HTR-8/SVneo cell lines were treated with LPS (20 ng/mL) to induce inflammatory responses in vitro, with selected miR-7, miR-150, miR-186 and miR-424. The expression was analyzed by qRT-PCR. As a result, expression of CRP was significantly increased in LPS-treated trophoblast (p<0.001) and miR-150 and miR-424 expression were significantly decreased (p<0.001). Thus, miR-150 and miR-424 are involved in the regulation of CRP expression in inflammatory-induced trophoblast and may be useful for the prenatal diagnosis of inflammatory obstetric diseases.