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miR-302a-5p/367-3p-HMGA2 axis regulates malignant processes during endometrial cancer development.
J Exp Clin Cancer Res 2018; 37(1):19JE

Abstract

BACKGROUND

Metastasis 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.

METHODS

The 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.

RESULTS

In 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.

CONCLUSION

Our 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.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Shengjing Hospital of China Medical University, Shenyang, 110004, China.Department of Obstetrics and Gynecology, Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Shengjing Hospital of China Medical University, Shenyang, 110004, China.Department of Obstetrics and Gynecology, Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Shengjing Hospital of China Medical University, Shenyang, 110004, China.Department of Obstetrics and Gynecology, Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Shengjing Hospital of China Medical University, Shenyang, 110004, China.Department of Obstetrics and Gynecology, Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Shengjing Hospital of China Medical University, Shenyang, 110004, China.Department of Obstetrics and Gynecology, Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Shengjing Hospital of China Medical University, Shenyang, 110004, China. maxiaoxin666@aliyun.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29391048

Citation

Ma, Jian, et al. "MiR-302a-5p/367-3p-HMGA2 Axis Regulates Malignant Processes During Endometrial Cancer Development." Journal of Experimental & Clinical Cancer Research : CR, vol. 37, no. 1, 2018, p. 19.
Ma J, Li D, Kong FF, et al. MiR-302a-5p/367-3p-HMGA2 axis regulates malignant processes during endometrial cancer development. J Exp Clin Cancer Res. 2018;37(1):19.
Ma, J., Li, D., Kong, F. F., Yang, D., Yang, H., & Ma, X. X. (2018). MiR-302a-5p/367-3p-HMGA2 axis regulates malignant processes during endometrial cancer development. Journal of Experimental & Clinical Cancer Research : CR, 37(1), p. 19. doi:10.1186/s13046-018-0686-6.
Ma J, et al. MiR-302a-5p/367-3p-HMGA2 Axis Regulates Malignant Processes During Endometrial Cancer Development. J Exp Clin Cancer Res. 2018 Feb 1;37(1):19. PubMed PMID: 29391048.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - miR-302a-5p/367-3p-HMGA2 axis regulates malignant processes during endometrial cancer development. AU - Ma,Jian, AU - Li,Da, AU - Kong,Fan-Fei, AU - Yang,Di, AU - Yang,Hui, AU - Ma,Xiao-Xin, Y1 - 2018/02/01/ PY - 2017/09/25/received PY - 2018/01/23/accepted PY - 2018/2/3/entrez PY - 2018/2/3/pubmed PY - 2019/5/10/medline KW - EMT KW - Endometrial cancer KW - HMGA2 KW - Regulation KW - miRNAs SP - 19 EP - 19 JF - Journal of experimental & clinical cancer research : CR JO - J. Exp. Clin. Cancer Res. VL - 37 IS - 1 N2 - BACKGROUND: Metastasis 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. METHODS: The 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. RESULTS: In 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. CONCLUSION: Our 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. SN - 1756-9966 UR - https://www.unboundmedicine.com/medline/citation/29391048/miR_302a_5p/367_3p_HMGA2_axis_regulates_malignant_processes_during_endometrial_cancer_development_ L2 - https://jeccr.biomedcentral.com/articles/10.1186/s13046-018-0686-6 DB - PRIME DP - Unbound Medicine ER -