دانلود رایگان مقاله درگیری ریز RNA-200C در گسترش سرطان معده با سرکوب p27Kip1

Abstract

P27Kip1, also known as Cyclin-dependent kinase inhibitor 1B, is an important check-point protein in the cell cycle. It has been identified that although as a tumor suppressor, P27Kip1 is expressed in different cancer cell types, which shows the therapeutic potential in tumor genesis. In this study, we examined the upstream regulatory mechanism of P27Kip1 at the microRNA (miRNA) level in gastric carcinogenesis. We used bioinformatics to predict that microRNA-200c (miR-200c) might be a direct upstream regulator of P27Kip1. It was also verified in gastric epithelial-derived cell lines that overexpression of miR-200c significantly inhibited the expression levels of P27Kip1, whereas knockdown of miR-200c promoted P27Kip1 expression in AGS and BGC-823 cells. Furthermore, we identified the direct binding of miR-200c on the P27Kip1 3′ -UTR sequence by luciferase assay. MiR-200c could enhance the colony formation of cells by repressing P27Kip1 expression. In addition, the negative correlation between P27Kip1 and miR-200c in human gastric cancer tissues and matched normal tissues further supported the tumor-promoting action of miR-200c in vivo. Our finding suggested that miR-200c directly regulates the expression of P27Kip1 and promotes cell growth in gastric cancer as an oncogene, which may provide new clues to treatment.

4. Discussion

In this study, we showed that miR-200c played an oncogenetic role in human gastric carcinogenesis by directly downregulated the expression of P27Kip1 and promoted the gastric cancer cell proliferation. Gastric cancer (GC) is one of the most common human malignant diseases and the second leading cause of tumor-related deaths worldwide [1,2]. The incidence and mortality rate are particularly high in eastern Asia [3]. Despite recent advances in surgical techniques and adjuvant therapy after surgery, the 5-year survival rate is still low [25]. Carcinogenesis is a multi-factor, multi-phase and long-term interaction process on malignant transformation of normal cells. In this process, the abnormal regulation of cell cycle is involved in all the stages [26]. In previous studies, we have identified P27Kip1 is an important target which could be regulated by different factors in the proliferation of gastric cancer cells, including H. pylori infection, the escape of cancer cells senescence, epigenetics, et al. [13,14,27]. We also find that P27Kip1 can express in different cancer cell lines, which means it might be a valuable target for the diagnosis and treatment of gastric cancer.