The Expression And Significance Of HMOF Protein In Colorectal Cancer

Colorectal cancer (Colorectal cancer, CRC) is one of the most common malignant tumor inthe world, and it is effected in health seriously. CRC is a consequence of many factors, normalintestinal epithelium to complete deterioration would take many years or even decades. Includingmore and more molecular biology event occurs, such as DNA methylation, MYH (mutyh)mutation, deletion of IGF-II mark, serrated polyps and so on. The activation of oncogenes andthe inactivation of tumor suppressor genes also play an important role in the process of CRCoccurrence. Recent studies showed that epigenetics change was also one of the pathogenesis ofCRC. Epigenetics includes DNA methylation, histone modification, micRNA interference,however, the histone modification plays an important part in the regulation of cell cycle,chromatin remodeling, DNA repair and proteinexpression; Human MOF (human males absent onthe first, hMOF) is one of the members of histone acetyltransferase family, it has the function ofspecifically recognise acetylated H4K16and P53. Some research confirms that hMOF canparticipated in the functions include gene transcription, change of the conformation in chromatin,cell cycle regulation, repair of DNA damage, apoptosis and maintaining the nuclear structuredirect or indirect by the effects of acetylation. The study showed that, the expression of hMOF inrenal cell carcinoma, glioma, and other types of malignancies was significantly lower than that innormal tissue. With the increasing of grade malignancy, loss of hMOF expression is more obvious,it showed that loss of hMOF expression plays an important role in the process ofcellcarcinogenesis. At the same time the study also showed that the role of hMOF is inhibit theacetylation of histone H4K16. But at present the acetylation of hMOF and H4K16in thedevelopment of rectal cancer have not been reported.Our research aims to combined detect the expression hMOF and H4K16Ac in colorectalnormal mucosa, tubular adenoma tissue and colorectal carcinoma to analysis their correlation, andexplore the significance and the mechanism of their expression in rectal cancer.1. Experimental method(1)In this study, we used immunohistochemical staining SP two-step method detected theexpression level of hMOF and H4K16Ac protein in66cases of rectal cancer tissues and15casestubular adenoma to analyze the correlation with clinical index.(2)Western blot and QPCR were used to analyse the expression of hMOF in44cases of freshspecimens of rectal cancer and its normal mucosa tissue.(3)Statistical methods to analyse the correlation between the expression of hMOF andH4K16Ac in rectal cancer tissues. 2. Experimental results(1) The results of immunohistochemistry showed that hMOF was positively expressed withbrown, the staining was located in the nucleus. The rate of positive expression of hMOF innormal mucosa tissue, rectal tubular adenoma tissue and rectal cancer tissue were100%,93.3%,and34.9%. The expression of hMOF in normal mucosa tissue and rectal tubular adenoma tissueshowed no significant difference (P=0.06＞0.01). The expression of hMOF was significantlylower than the former (P=0.000＜0.01，P=0.001＜0.01). The expression of hMOF hassignificantly positive correlation with tumors stage, pathological differentiation and lymph nodemetastasis (P=0.007＜0.01，P=0.036＜0.01，P=0.004＜0.01).(2) The results of Western blot and QPCR showed that the expression of hMOF andH4K16Ac in rectal cancer tissues was significantly lower than that in fresh normal mucosa.(P=0.008＜0.01,P=0.03＜0.05).(3) The rate of positive expression of H4K16Ac in normal mucosa tissue, rectal tubularadenoma tissue and rectal cancer tissue was100%,80%,42.4%. The expression of H4K16Ac innormal mucosa tissue and rectal tubular adenoma tissue showed no significant difference(P=0.094＞0.01). The expression of H4K16Ac was significantly lower than the former(P=0.000＜0.01，P=0.004＜0.01). The expression of hMOF has significantly positive correlationwith pathological differentiation (P=0.000＜0.01).(4) The statistical results showed that the expression of hMOF and H4K16Ac havesignificantly positive correlation in rectal cancer tissues (P=0.000＜0.01).3. conclusion(1) The expression of hMOF protein in colorectal carcinoma was lower and the expressionwas decrease with the increase of pathological differentiation and tumors stage, and it wasnegatively correlated with lymph node metastasis;(2) The expression of H4K16Ac protein in colorectal carcinoma was lower; and theexpression was decrease with the increase of pathological differentiation;(3) hMOF protein was positively correlated with H4K16Ac protein in the tissue of colorectalcarcinoma.