Collagen prolyl hydroxylase 3 has a tumor suppressive activity in human lung cancer.

Collagen prolyl hydroxylases (P3H) are required for proper collagen biosynthesis. One of the family members P3H3 was downregulated in breast cancer and lymphoma due to DNA methylation. However the role of P3H3 in lung cancer has not yet been elucidated. In this study, we analyzed P3H3 expression in a panel of lung cancer cell lines and primary lung tumors. Epigenetic regulation was explored and the function of P3H3 was investigated by stable transfection and RNA interference. We found that P3H3 was downregulated in 6 out of 10 lung cancer cell lines. A heterogeneous methylation pattern of P3H3 was found in the exon region. In primary lung tumors, immunohistochemistry on tissue microarray (TMA) showed that higher expression of P3H3 was significantly associated with lower tumor N stage and grade (p = 0.035 and p = 0.026, respectively). Ectopic expression of P3H3 inhibited cell proliferation, colony formation, migration as well as invasion, and induced apoptosis together with cell cycle arrest in the G2/M phase. Knockdown of P3H3 led to increased migratory and invasive potential. These Phenomena are accompanied by enhanced p21, decreased cyclin A1 levels and increased caspase 3/7 activities. Taken together, we feel that P3H3 is a novel tumor suppressor and its protein expression is inversely related to lymph node metastasis and tumor differentiation in lung cancer.

Role of ZNF334 in cervical cancer: implications for EMT reversal and tumor suppression.

Zinc-finger proteins are involved in many biological processes. However, the role of Zinc-finger protein 334 (ZNF334) in cervical cancer remains unidentified. This study showed that promoter methylation of ZNF334 was responsible for its reduced expression. ZNF334 suppressed malignant biological behaviors in cervical cancer. Notably, ZNF334 reversed the EMT process both in vitro and in vivo. RNA-seq coupled with bioinformatics analysis caught P3H3 which is upregulated by ZNF334. Dual-luciferase reporter and Chromatin immunoprecipitation assays illustrated that ZNF334 directly regulate P3H3. Knockdown of P3H3 attenuated the reversal of EMT induced by ZNF334. Additionally, ZNF334 overexpression sensitized cervical cancer cells to the cytotoxic effects of paclitaxel, cyclosporine and sunitinib. In conclusions, this study illustrated that DNA methylation-based silencing ZNF334 played a vital role in cervical cancer, by regulating P3H3 in turn affects EMT. ZNF334 has the potential to become a novel diagnostic biomarker and a potential treatment target for cervical cancer.