Genomic imbalances are involved in miR-30c and let-7a deregulation in ovarian tumors: implications for <i>HMGA2</i> expression

Agostini, Antonio; Brunetti, Marta; Davidson, Ben; Tropé, Claes G.; Heim, Sverre; Panagopoulos, Ioannis; Micci, Francesca

doi:10.18632/oncotarget.15795

Cited by 15 publications

(9 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, more and more studies have indicated that microRNAs are associated with tumorigenesis and development and that microRNAs play important roles in a variety of biological processes; their dysregulation may be crucial to cancer initiation, progression and treatment outcome . Some microRNAs were also reported to be associated with BC.…”

Section: Discussionmentioning

confidence: 99%

Association of miR‐1247‐5p expression with clinicopathological parameters and prognosis in breast cancer

Zhang

Fan

et al. 2018

Int J Experimental Path

View full text Add to dashboard Cite

SummaryOur study aimed to clarify the correlation between miR‐1247‐5p expression and clinicopathological parameters and survival of patients with breast cancer (BC). We evaluated the expression level of miR‐1247‐5p in 224 formalin‐fixed, paraffin‐embedded specimens (112 BC and matched cancer free tissues) by quantitative real‐time reverse transcriptase polymerase chain reaction (qRT‐PCR). miR‐1247‐5p expression in BC tissues was found to be decreased compared with matched normal tissues (P < 0.01). Additionally, low miR‐1247‐5p expression in BC tissues was significantly associated with the advanced TNM stage (P = 0.007), lymph node metastasis (P = 0.015), poorer pathological differentiation (P = 0.005) and molecular subtype (P = 0.027). The patients in the low miR‐1247‐5p group had a shorter disease‐free survival and overall survival than those in the high miR‐1247‐5p group (P < 0.01). Furthermore, the univariate and the multivariate analyses showed that miR‐1247‐5p expression was an independent predictor of overall survival (P < 0.01). Our study showed that miR‐1247‐5p was related to the biological behaviour of breast tumour and prognosis of patients with BC. miR‐1247‐5p could be a novel tumour suppressor and act as a potential biomarker and therapeutic agent for breast carcinoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Association of miR‐1247‐5p expression with clinicopathological parameters and prognosis in breast cancer

Zhang

Fan

et al. 2018

Int J Experimental Path

View full text Add to dashboard Cite

show abstract

“…In addition, the expression of the HMGA2 is associated with tumour stage and clinical outcomes in ovarian carcinoma [ 8 ]. As an oncogene, HMGA2 regulates cell proliferation, the cell cycle and apoptosis, and it is involved in the regulation of invasion and metastasis, which are key processes in tumour progression, such as ovarian tumours [ 9 ], breast adenocarcinoma [ 10 ] and lung cancers [ 11 ]. Until now, it has been reported that HMGA2 is highly expressed in endometrial cancer tissues and that the overexpression of HMGA2 promotes tumour growth and metastasis [ 12 ].…”

Section: Introductionmentioning

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

“…Previous studies have reported the involvement of HMGA2 in different steps of tumorigenesis. High levels of HMGA2 are reported in various cancer types, including ovarian cancer [ 10 , 15 ]. To determine whether HMGA2 is involved in miR-219-5p activity on tumor cell proliferation, an HMGA2 overexpression vector was constructed and successfully transfected into SKOV3 cells.…”

Section: Resultsmentioning

confidence: 99%

“…The protein modulates multiple genes through effects on protein-DNA or protein–protein interactions [ 4 , 5 ]. HMGA2 has been identified as an oncoprotein that is frequently upregulated in a variety of cancers, including breast cancer [ 6 ], esophageal squamous carcinoma [ 7 ], colorectal cancer [ 8 , 9 ], ovarian tumors [ 10 ]. However, the mechanisms underlying regulation of HMGA2 in ovarian tumors are currently unclear.…”

Section: Introductionmentioning

confidence: 99%

MiR-219-5p inhibits growth and metastasis of ovarian cancer cells by targeting HMGA2

Feng

Song

2018

Biol Res

View full text Add to dashboard Cite

BackgroundAccumulating studies have demonstrated that high-mobility group A2 (HMGA2), an oncofetal protein, plays a role in tumor development and progression. However, the molecular role of HMGA2 in ovarian carcinoma is yet to be established. MicroRNAs (miRNAs), a group of small noncoding RNAs, negatively regulate gene expression and their dysregulation has been implicated in tumorigenesis. The aim of this study was to investigate the potential involvement of a specific miRNA, miR-219-5p, in HMGA2-induced ovarian cancer.MethodsThe ovarian cancer cell line, SKOV3, was employed, and miR-219-5p and HMGA2 overexpression vectors constructed. The CCK-8 kit was used to determine cell proliferation and the Transwell® assay used to measure cell invasion and migration. RT-PCR and western blot analyses were applied to analyze the expression of miR-219-5p and HMGA2, and the luciferase reporter assay used to examine the interactions between miR-219-5p and HMGA2. Nude mice were employed to characterize in vivo tumor growth regulation.ResultsExpression of miR-219-5p led to suppression of proliferation, invasion and migration of the ovarian cancer cell line, SKOV3, by targeting HMGA2. The inhibitory effects of miR-219-5p were reversed upon overexpression of HMGA2. Data from the luciferase reporter assay showed that miR-219-5p downregulates HMGA2 via direct integration with its 3′-UTR. Consistent with in vitro findings, expression of miR-219-5p led to significant inhibition of tumor growth in vivo.ConclusionOur results collectively suggest that miR-219-5p inhibits tumor growth and metastasis by targeting HMGA2.

show abstract

Genomic imbalances are involved in miR-30c and let-7a deregulation in ovarian tumors: implications for HMGA2 expression

Cited by 15 publications

References 30 publications

Association of miR‐1247‐5p expression with clinicopathological parameters and prognosis in breast cancer

Association of miR‐1247‐5p expression with clinicopathological parameters and prognosis in breast cancer

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

MiR-219-5p inhibits growth and metastasis of ovarian cancer cells by targeting HMGA2

Contact Info

Product

Resources

About