Abstract
Well-run screening programs for cervical cancer in the population at risk have been shown to result in a sharp decrease in the incidence and mortality of cervical cancer in a number of large populations. Expression patterns of a recently identified biomarker family, microRNA, appear to be characteristic of tumor type and developmental origin. Several tumors have been reported to actively release exosomes carrying microRNAs. The present study has determined the association of microRNAs with cervical cancer-derived exosomes. The cervical cancer-derived exosomes were enriched in the cervicovaginal lavages specimens and the abundance of exosomes and exosomal microRNAs was detected by electron microscopy, western blot analysis, RT-qPCR and microRNA target reporter vector. The microRNA-21 and microRNA-146a, which were up-regulated in cervical cancer patients, were associated with the high levels of cervical cancer-derived exosomes. In conclusion, we demonstrated the abundance of exosomes in the cervicovaginal lavage specimens of women with cervical cancer. Furthermore, our results indicated that abnormally high levels of microRNA-21 and microRNA-146a existed in the cervical cancer-derived exosomes and the two microRNAs were functional in 293T cells.
Highlights
Cervical cancer (CC) is one of main causes of cancer-related death in women [1] and the third most common cancer among women worldwide [2]
Cervicovaginal lavages specimens were collected from 45 patients with cervical cancers, 25 HPV-positive subjects and 32 normal HPV-negative subjects
The pellets were spherical in shape, with an average diameters varying between 30 and 110 nm (Figure 1A), consistent with the previously reported characteristics of exosomes [37]
Summary
Cervical cancer (CC) is one of main causes of cancer-related death in women [1] and the third most common cancer among women worldwide [2]. Persistent cervical infection with high-risk HPV genotypes contributes to the development of cervical cancer [3], the cervical intraepithelial neoplasia (CIN) [4], and the pre-cancer of the cervix. The most carcinogenic HPV type 16 (HPV16) and the second most carcinogenic HPV18 account for more than 60% of all cervical cancers [6,7]. The establishment of the causal link between HPV and cervical cancer, along with an understanding of the HPV infection history, have refreshed the model for cervical carcinogenesis: persistent HPV infection progresses to pre-cancer and eventually causes cancer (in situ and invasive) [8]. Several cofactors, including dysregulation of microRNAs, have been implicated in the genesis of HPV-associated cervical cancer [9,10]
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