Research Of The Influence Of KIAA1429 On The Expression And Cell Function Of Colorectal Cancer

Background: Globally,colorectal cancer（CRC）is the third most common type of cancer.The development of colorectal cancer is a multi-step and multi-mechanism process involving activation of oncogenes and inactivation of tumor suppressor genes,including both genetically-altered genome changes and epigenetic changes.Abnormal epigenetic changes are also important in the development of tumors.In recent years,RNA methylation modifications involved in the regulation of gene transcriptome have gradually become the focus of epigenetic studies,and the relationship with malignant tumors has also received more and more attention and research.Methylation modification of adenine（A）—m6A,which occurs in RNA,lnc RNA,etc.,is regulated by m6 A modification enzymes（methyltransferase and demethylase）in a dynamically reversible manner.Currently,the major methyltransferases（“Writers”）have been found: methyltransferase-like 3（METTL3）,methyltransferase-like protein14（METTL14）,wilms tumor 1-associating protein（WTAP）and KIAA1429.Demethylase（“Erasers”）mainly includes fat mass and obesity associated protein（FTO）and Alk B homolog 5（ALKBH5）.In addition,m6A-binding proteins（“Readers”）,such as YTH domain-containing family protein 1（YTHDF1）,YTH domain-containing family protein 2（YTHDF2）,YTH domain-containing protein 1（YTHDC1）and Heterogeneous nuclear ribonucleoproteins A2B1（HNRNPA2B1）,can specifically bind to m6 A and mediate their biological functions.Abnormal expression of m6 A methylase and demethylase is an important factor leading to abnormal content of m6 A,which plays an important role in the tumorigenesis and development of malignant tumors.Our previous research found that the methyltransferase KIAA1429 may play a key role in abnormal content of m6 A in breast cancer.A series of in vitro functional experiments also found that overexpression of KIAA1429 could promote the proliferation,migration and invasion of breast cancer cells.Further studies showed that KIAA1429 could play its role by binding to cyclin dependent kinase 1（CDK1）.At present,there has been no report about KIAA1429 and colorectal cancer.Methods: We used quantitative real-time reverse transcription polymerase chain reaction（q RT-PCR）and Western Blot（WB）to detect the m RNA and protein expression level of KIAA1429 in colorectal cancer and para-cancer tissues.Lentivirus transfection technique was used to establish over-expression and down-expression of KIAA1429 in colorectal cancer cell lines,which was used to explore the function of KIAA1429 in proliferation,metastasis and invasion of cells by CCK-8 assay,colony formation assay,scratch-wound assay,and transwell migration and invasion assay.We also performed xenograft studies using nude mice in vivo.Results: Compared to the para-cancer tissues,the m RNA expression of KIAA1429 was significantly higher in 43 cases of colorectal cancer tissues（P < 0.05）.Cell function experiments showed that KIAA1429 could promote the proliferation,invasion and migration of colorectal cancer cells.The xenograft studies using nude mice in vivo verified the above results.Conclusion: KIAA1429 is highly expressed in colorectal cancer tissues and it promotes the proliferation,migration and invasion of colorectal cancer cells.That is,KIAA1429 plays an oncogene role in colorectal cancer.The results of this study can provide clues for the further mechanism research and clinical application of KIAA1429 in colorectal cancer.