miR-3156-3p is downregulated in HPV-positive cervical cancer and performs as a tumor-suppressive miRNA
| Autor: | Hai-Xia Liu, Ning Wang, Fu-Fen Yin, Gui-Hua Pei, Yan-Ci Che, Yu-Fang Xia, Bing Luo, Yankui Wang, Fengsheng Yu |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Human papillomavirus Microarray Uterine Cervical Neoplasms SLC6A6 Flow cytometry HeLa 03 medical and health sciences 0302 clinical medicine Virology microRNA medicine Humans Genes Tumor Suppressor Cells Cultured Tube formation biology medicine.diagnostic_test Gene Expression Profiling Research HPV infection Cancer Microarray Analysis biology.organism_classification medicine.disease MicroRNAs 030104 developmental biology Infectious Diseases Gene Expression Regulation Cell culture 030220 oncology & carcinogenesis Cervical cancer Female |
| Zdroj: | Virology Journal |
| ISSN: | 1743-422X |
| DOI: | 10.1186/s12985-017-0695-7 |
| Popis: | Background Cervical cancer (CC) is the second most common cancer in females in developing countries. The two viral oncoproteins E6 and E7 mediate the oncogenic activities of high-risk human papillomavirus (HR-HPV), and HR-HPV, especially HPV16 or/and HPV18 (HPV16/18) play critical roles in CC through different pathways. microRNAs (miRNAs) may be associated with CC pathogenesis. Researches have indicated that human papillomavirus (HPV) may regulate cellular miRNA expression through viral E6 and E7. Herein, the purposes of this study were to identify the relationship between HPV infection and aberrantly expressed miRNAs and to investigate their pathogenic roles in CC. Methods miRNA expression was assessed using a microRNAs microarray in HPV16 E6- and E7-integrated HPV-negative HT-3 cell lines and mock vector-transfected HT-3 cells. The microarray results were validated, and the expression of miR-3156-3p was identified in HPV-positive and -negative CC cell lines as well as primary CC and normal cervical epithelium tissues using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK8), flow cytometry, transwell analysis, tube formation, and Western blotting were used to identify the functional role of miR-3156-3p in CaSki, SiHa, and HeLa cell lines. Results Six underexpressed microRNAs (miR-3156-3p, 6779-3p, 4779-3p, 6841-3p, 454-5p and 656-5p) were consistently identified in HPV16 E6- and E7-integrated HT-3 cells. Further investigation confirmed a significant decrease of miR-3156-3p in HPV16/18 positive CC lesions. CCK8, flow cytometry, transwell analysis, tube formation assays, and Western blotting of the CC cell lines with miR-3156-3p over/under-expression in vitro showed that miR-3156-3p was involved in cell proliferation, apoptosis, migration, neovascularization, and SLC6A6 regulation. Conclusions Our findings indicate that miR-3156-3p plays a suppressor-miRNA role in CC and that its expression is associated with HR-HPV infection. |
| Databáze: | OpenAIRE |
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