High-risk human papillomavirus (HPV) type 16, which is responsible for greater than 50% of cervical cancer cases, is the most prevalent and lethal HPV type. However, the molecular mechanisms of cervical carcinogenesis remain elusive, particularly the early steps of HPV infection that may transform normal cervical epithelium into a pre-neoplastic state. Here, we report that a group of microRNAs (microRNAs) were aberrantly decreased in HPV16-positive normal cervical tissues, and these groups of microRNAs are further reduced in cervical carcinoma. Among these miRNAs, miR196a expression is the most reduced in HPV16-infected tissues. Interestingly, miR196a expression is low in HPV16-positive cervical cancer cell lines but high in HPV16-negative cervical cancer cell lines. Furthermore, we found that only HPV16 early gene E5 specifically down-regulated miRNA196a in the cervical cancer cell lines. In addition, HoxB8, a known miR196a target gene, is up-regulated in the HPV16 cervical carcinoma cell line but not in HPV18 cervical cancer cell lines. Various doses of miR196a affected cervical cancer cell proliferation and apoptosis. Altogether, these results suggested that HPV16 E5 specifically down-regulates miR196a upon infection of the human cervix and initiates the transformation of normal cervix cells to cervical carcinoma.

No abstract

COC166-9 is an ovarian cancer-specific monoclonal antibody, and COC166-9-based immunotherapy has been shown to possess killing effects against ovarian cancer cells in vitro and in vivo. However the antigen recognized by COC166-9 (COC166-9-Ag, CA166-9) has not been identified and the clinical significance of CA166-9 expression remains unknown. We found that CA166-9 was positive in 53.1% of ovarian cancer tissues. Expression of CA166-9 was strongly correlated with the cancer recurrence (P<0.001). Patients with positive CA166-9 had substantially shorter overall survival (P=0.026) and disease-free survival (P=0.002). CA166-9 was also shown to be an independent predictive factor for overall survival (HR=2.454, P=0.016) and disease-free survival (HR=2.331, P=0.021). We identified CA166-9 as human immunoglobulin γ-1 heavy chain constant region (IGHG1). Purified IGHG1 promoted proliferation, migration, and invasion of CA166-9-negative ovarian cancer HOC1A cells, whereas it had minimal effects on the phenotypes of CA166-9-positive ovarian cancer CAOV-3 cells. In addition, overexpression of IGHG1 enhanced migration of ovarian cancer cells. On the contrary, COC166-9 inhibited proliferation, migration, and invasion of CAOV-3 cells, but had no effects on HOC1A cells. Therefore, IGHG1 similarly to CA166-9, could play an important role in ovarian cancer development and may serve as a potential prognostic marker and a therapeutical target for ovarian cancer.

No abstract