| Cancer has become the leading cause of death and vitally important public health problem in our country, and the estimated incidence and mortality of cancer is 4.292 million and 2.814 million in 2015, about 12 thousand people diagnosed cancer and 7.5 thousand people died of cancer everyday. Multiple myeloma(MM) is a common hematological malignant tumor with the characteristics of cloning reproduction of neoplastic plasma cells in bone marrow, and the traditional treatments of MM such as autologous stem cell transplantation and chemotherapy do not obtain good therapeutic benefit. As one of the most common malignant tumors in women, cervical cancer has higher mortality and morbidity in recent years.Esophageal carcinoma is always one of the four tumors with highest morbidity and mortality in China. In general, the treatment for tumor progression and early detection is yet to be further exploration and research.However, epigenetics provides the possibly developmental direction for the early detection, treatment and prognosis of cancer. DNA methylation, animportant epigenetic regulatory mechanism, has clinical significance for the early diagnosis and prognosis judgement in multiple cancers.Krüppel-associated box zinc finger protein(KRAB-ZFPs) is the most common type of transcriptional factors. Zinc finger protein 545(ZNF545)is one of KRAB-ZFP family members. Published articles have reported that ZNF545 had different levels of methylation and decreased expression in gastric cancer, nasopharyngeal carcinoma, esophageal cancer, colon cancer,cervical cancer and breast cancer etc., and may have significantly biological functions for inhibiting tumor growth, but it has not been reported in multiple myeloma, and its functional mechanism in cervical and esophageal cancer is unclear. Thus, we speculated that ZNF545 may be a candidate tumor suppressor gene in the development of multiple myeloma,cervical cancer and esophageal cancer tumor. The present study analyzes the different expression of ZNF545 and its methylation status in multiple myeloma, cervical cancer and esophageal cancer cell lines, their tumor tissues and matched normal tissues by the methods of reverse transcription polymerase chain reaction(RT-PCR), real-time fluorescence quantitative polymerase chain reaction(real-time PCR), methylation specific polymerase chain reaction(MSP), Western blot(WB) and online database.The 5-nitrogen heterocyclic-2-deoxidation cytidine(5-Aza-dC) combined with acetylated histone inhibitor trichostatin A(TSA) treats the cancer cell lines with silenced or downregulated ZNF545. We also investigate theeffects of ZNF545 on proliferation and apoptosis of multiple myeloma,cervical cancer and esophagus cancer cell lines through in vitro experiments including soft agar CFA or plate CFA assay, MTS assay and the flow cytometry of Annexin V-FITC/PI stain, and further detect its effects on p53 signaling pathway by quantitative PCR and WB. The results show that the expression levels of ZNF545 in multiple myeloma, cervical cancer and esophageal cancer tissues or cell lines were differently silenced or downregulated with compared to the normal tissues or adjacent normal tissues. The recovery of mRNA expression of ZNF545 in cancer methylation cell lines was detected after demethylation treatment. At the same time, the promoter methylation of ZNF545 exists in multiple myeloma cell lines(KM3 and RPMI8226), cervical cancer cell line(Hela),esophageal cancer cell line(KYSE150), and 28.3%(13/46) in multiple myeloma, 76.6%(49/64) in the esophageal cancer tissues. In vitro experimental results indicate that ZNF545 can function its suppressive effects on tumor cell growth by effectively inhibiting cell proliferation and inducing apoptosis, and further find that its suppressive functions on tumor cells are realized through transcriptional activation of p53 signaling pathway.In conclusion, as a tumor suppressor gene, ZNF545 is involved in the development of multiple myeloma, cervical cancer and esophageal cancer,and which further provide certain theoretical basis for finding thebiomarkers of early diagnosis, prognosis and targeted therapy in human cancer. |
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