MicroRNA-302a inhibits cell proliferation and invasion, and induces cell apoptosis in hepatocellular carcinoma by directly targeting VEGFA

Qin, Chenglin; Zha, Wenzhang; Fan, Rengen; Ding, Huimin; Xu, Yong-Hua; Wang, Chen

doi:10.3892/mmr.2017.7312

Cited by 18 publications

(21 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…qRT-PCR, Western blot and luciferase reporter assay results confirmed that VEGFA was a direct target of miR-302 cluster. These findings were consistent with a previous study in which Qin et al reported that miR-302a inhibited hepatocellular carcinoma cell proliferation and invasion through targeting VEGFA 32. We further revealed that there was a negative correlation between miR-302 cluster and VEGFA mRNA level in CML patients.…”

Section: Discussionsupporting

confidence: 93%

miR-302 cluster inhibits angiogenesis and growth of K562 leukemia cells by targeting VEGFA

Cao¹,

Li²,

Han³

et al. 2019

OTT

View full text Add to dashboard Cite

BackgroundmiR-302 cluster has been reported as a tumor suppressor in many human cancers; yet, its function in chronic myeloid leukemia (CML) tumorigenesis remains largely unclear. The study was aimed to explore the functional roles of miR-302 cluster in CML progression.Materials and methodsQuantitative reverse transcriptase PCR and Western blot were performed to evaluate miR-302 cluster and vascular endothelial growth factor A (VEGFA) expression levels. Cell Counting Kit-8 assay, colony formation assay and human umbilical vein endothelial cell line capillary tube formation were used to determine the influence of miR-302 cluster on the growth and angiogenesis of K562 cells, respectively. Luciferase reporter assay was employed to confirm the direct target interaction between miR-302 cluster and VEGFA.ResultsThis study demonstrated that miR-302 cluster was frequently downregulated in CML samples and cell lines and high level of miR-302 cluster was significantly associated with good prognosis of CML patients. Compared with miRNA negative control, miR-302 cluster mimics obviously suppressed cell growth, colony formation and angiogenesis. Further studies revealed that VEGFA was a direct target gene of miR-302 cluster. Moreover, overexpression of VEGFA dramatically abated the inhibition of miR-302 cluster on cell growth and angiogenesis.ConclusionThe present study, for the first time, identified miR-302 cluster as a tumor suppressor, and overexpression of miR-302 cluster inhibited growth and angiogenesis in K562 cells. miR-302 cluster may be a potential therapeutic target in CML to develop the adjuvant antiangiogenic therapy based on VEGFA.

show abstract

Section: Discussionsupporting

confidence: 93%

miR-302 cluster inhibits angiogenesis and growth of K562 leukemia cells by targeting VEGFA

Cao¹,

Li²,

Han³

et al. 2019

OTT

View full text Add to dashboard Cite

show abstract

“…In addition, knockdown of HMGA2 expression, increased the expression of miR-302a-5p/367-3p. Besides HMGA2, miR-302a or miR-367-3p may target multiple genes and pathways to inhibit tumour growth and metastasis [ 43 , 44 ]. This indicates that the combination of agomirs and target genes may be more effective in the inhibition of tumour growth in vitro.…”

Section: Discussionmentioning

confidence: 99%

miR-302a-5p/367-3p-HMGA2 axis regulates malignant processes during endometrial cancer development

Kong

et al. 2018

J Exp Clin Cancer Res

View full text Add to dashboard Cite

BackgroundMetastasis is one of the main reasons for treatment failure in endometrial cancer. Notably, high mobility group AT-hook 2 (HMGA2) has been recognized as a driving factor of tumour metastasis. microRNAs (miRNAs) are powerful posttranscriptional regulators of HMGA2.MethodsThe binding sites of miR-302a-5p and miR-367-3p on HMGA2 mRNA were identified using bioinformatics prediction software and were validated via luciferase assay. The expression levels of miR-302a-5p and miR-367-3p were detected using quantitative real-time PCR and in situ hybridization. Western blotting and immunohistochemistry were used to detect the levels of HMGA2 and epithelial-mesenchymal transition pathway-related proteins. Co-immunoprecipitation was used to detect protein interactions. The roles of miR-302a-5p and miR-367-3p in the regulation of HMGA2 during the progression of endometrial cancer were investigated using both in vitro and in vivo assays.ResultsIn the present study, high HMGA2 expression was correlated with poor clinical outcomes in endometrial cancer. The binding sites of miRNAs on HMGA2 mRNA were identified using bioinformatics prediction software and were validated via luciferase assay. In the endometrial cancer cell lines Ishikawa and HEC-1A, the overexpression of miR-302a-5p/367-3p significantly inhibited the expression of HMGA2 mRNA. In endometrial cancer tissues, we showed that miR-302a-5p and miR-367-3p were significantly downregulated and thus inversely correlated with HMGA2. The miR-302a-5p and miR-367-3p expression levels were closely correlated with FIGO stage and lymph node metastasis. High expression of miR-302a-5p/367-3p was correlated with high survival rates in endometrial cancer. In addition, miR-302a-5p/367-3p suppressed the malignant behaviour of endometrial carcinoma cells via the inhibition of HMGA2 expression.ConclusionOur findings indicate that miR-302a-5p/367-3p-mediated expression of HMGA2 regulates the malignant behaviour of endometrial carcinoma cells, which suggests that the miR-302a-5p/367-3p-HMGA2 axis may be a predictive biomarker of endometrial cancer metastasis and patient survival and a potential therapeutic target in metastatic endometrial cancer.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0686-6) contains supplementary material, which is available to authorized users.

show abstract

“…Our previous study showed that tumor necrosis was related to advanced stage and worse survival in rectal cancer patients ( 48 ), and WRAP53 level was significantly increased in primary tumor compared to normal mucosa, which was associated with poor prognosis ( 39 ). In fact, the reduced expression of miR-302a has been frequently reported in several types of malignancies, such as breast cancer ( 21 ), HCC ( 22 ), prostate cancer ( 23 ), cervical cancer ( 24 ), and skin cancer ( 25 , 26 ). However, miR-302a was found to be overexpressed in CRC ( 20 , 28 , 29 ).…”

Section: Discussionmentioning

confidence: 99%

“…The downregulation of miR-302a in breast cancer cells plays an important role in regulation of invasion and metastasis of breast cancer ( 21 ). The low expression of miR-302a inhibits cell proliferation and invasion and induces cell apoptosis in HCC by directly targeting vascular endothelial growth factor-A ( 22 ). The overexpression of miR-302a in prostate cancer cells can induce cell cycle arrest and inhibit cell proliferation in vitro and tumor formation in vivo ( 23 ).…”

Section: Introductionmentioning

confidence: 99%

Expressions of miR-302a, miR-105, and miR-888 Play Critical Roles in Pathogenesis, Radiotherapy, and Prognosis on Rectal Cancer Patients: A Study From Rectal Cancer Patients in a Swedish Rectal Cancer Trial of Preoperative Radiotherapy to Big Database Analyses

et al. 2020

View full text Add to dashboard Cite

Differential expressions and functions of various micoRNAs (miRNAs) have been intensively studied in both colon and rectal cancers. However, the importance of miRNAs on radiotherapy (RT) response and clinical outcome in rectal cancer patients remains unclear. In this study, we used real-time polymerase chain reaction to examine the expressions of miR-302a, miR-105, and miR-888 in normal mucosa and cancer tissue from rectal cancer patients with and without preoperative RT. The biological function of miR-302a, miR-105, and miR-888 expression was further analyzed and identified through the public databases: TCGA (The Cancer Genome Atlas) and GEPIA (Gene Expression Profiling Interactive Analysis). The results showed that the expression of miR-105 in rectal cancer was higher than that in normal mucosa in RT ( P = 0.042) and non-RT patients ( P = 0.003) and was associated with mucinous histological type ( P = 0.004), COX-2 ( P = 0.042), and p73 expression ( P = 0.030). The expression of miR-302a was shown more frequently in cancers with necrosis ( P = 0.033) and with WRAP53 expression ( P = 0.015), whereas miR-888 expression occurred more frequently in tumors with protein the expression of survivin ( P = 0.015), AEG-1 (astrocyte elevated gene-1) ( P = 0.003), and SATB1 (special AT-rich sequence binding protein 1) ( P = 0.036). Moreover, TargetScan also predicted AEG-1 and SATB1 as putative targets for miR-888. The miRNA–gene network analysis showed that ABI2 was associated with all the three miRNAs, with lower expression and good diagnostic value in rectal cancers. The TCGA database demonstrated the association of miR-105 expression with high carcinoembryonic antigen level ( P = 0.048). RT reduced the expressions of miR-302a, miR-105, and miR-888. Prognostic analysis showed that miR-888 expression was independently associated with worse survival of patients without RT [overall survival, P = 0.001; disease-free survival, P = 0.009]. Analysis of biological function revealed that the protein serine/threonine kinase activity and PI3K-AKT signaling pathway were the most significantly enriched functions and pathways, respectively. Our findings suggest that miR-105 is involved in rectal cancer pathogenesis and miR-888 is associated with prognosis. MiR-302a, miR-105, and miR-888 have potential influence on the pathogenesis, RT, and prognosis of rectal cancer.

show abstract

MicroRNA-302a inhibits cell proliferation and invasion, and induces cell apoptosis in hepatocellular carcinoma by directly targeting VEGFA

Cited by 18 publications

References 35 publications

miR-302 cluster inhibits angiogenesis and growth of K562 leukemia cells by targeting VEGFA

miR-302 cluster inhibits angiogenesis and growth of K562 leukemia cells by targeting VEGFA

miR-302a-5p/367-3p-HMGA2 axis regulates malignant processes during endometrial cancer development

Expressions of miR-302a, miR-105, and miR-888 Play Critical Roles in Pathogenesis, Radiotherapy, and Prognosis on Rectal Cancer Patients: A Study From Rectal Cancer Patients in a Swedish Rectal Cancer Trial of Preoperative Radiotherapy to Big Database Analyses

Contact Info

Product

Resources

About