Abstract
BackgroundCervical 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.MethodsmiRNA 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.ResultsSix 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.ConclusionsOur findings indicate that miR-3156-3p plays a suppressor-miRNA role in CC and that its expression is associated with HR-HPV infection.
Highlights
Cervical cancer (CC) is the second most common cancer in females in developing countries
Identification of miR-3156-3p as an aberrantly expressed miRNA in high-risk human papillomavirus (HR-human papillomavirus (HPV)) infected CC The transfection efficiency was tested by western blotting, which revealed that the transfected cells successfully expressed the E6, −E7, or -E6/E7 proteins (Fig. 1a)
Our findings suggest that miR-3156-3p probably contributes to cervical carcinogenesis and its reduction of miR-3156-3p expression in cervical cancer might be associated with HR-HPV infection
Summary
Cervical cancer (CC) is the second most common cancer in females in developing countries. Researches have indicated that human papillomavirus (HPV) may regulate cellular miRNA expression through viral E6 and E7. Xia et al Virology Journal (2017) 14:20 after processing They primarily act as negative regulators of gene expression by binding to their complementary mRNA targets and either repressing translation or promoting mRNA degradation. Many studies indicate that changes in the expression of miRNAs may be associated with a variety of human cancers. These abnormally expressed miRNAs affect the expression of various oncogenic or tumor suppressor proteins that, in turn, alter cellular growth, invasion, and the metastatic potential of CC cells [4]. To date, mounting evidence indicates that HPVs may regulate cellular miRNA expression through viral E6 and E7 [6]
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