How ever, another study described the down regulation of tumor suppressor p53 by miR 33, suggesting a com plex and possible context dependent response to miR 33 manipulations. As p53 is often mutated in OS, it is unlikely that miR 33a promotes OS chemoresistance through down regulating p53 induced apoptosis. Thus, the enhancing effect of miR 33a on OS chemoresistance via down regulating TWIST expression is a new function of this miR, and the miR 33a TWIST signaling could be a novel mechanism involved in development of OS chemoresistance. There are some limitations of this study, This study was only performed in pediatric OS patients. Despite that adult OS patients only occupy a small portion of total OS patients, it would still be interesting to verify the findings in adult patients in future studies.
Cisplatin elicits DNA repair mechanisms by crosslinking DNA, which in turn activates apoptosis when repair proves impossible. In this study, we only examined the effect of miR 33a TWIST signaling on OS cell resistance to cisplatin. It is unclear whether miR 33a TWIST would impact OS cell resistance to other types of chemotherapy agents. Further studies with more types full article of chemotherapy agents and OS cell lines would elaborate this issue. In conclusion, we demonstrate that miR 33a is up regulated in chemoresistant OS and that the miR 33a level is negatively correlated with the TWIST protein level and the tumor necrosis rate in OS. Our in vitro data indicate that miR 33a promotes OS cell resist ance to cisplatin by down regulating TWIST, on the other hand, inhibition of miR 33a by antagomir 33a enhances cisplatin induced apoptosis in OS cells by up regulating TWIST expression.
The findings suggest that inhibition of miR 33a TWIST signaling could be a potential new strategy to enhance neoadjuvant chemotherapy for OS. Introduction Colorectal cancer is the third most commonly di agnosed cancer worldwide kinase inhibitor GNE-0877 with over 1. 4 million new cancer cases and 0. 6 million estimated deaths every year. The incidence of CRC has rapidly increased in China and other Asian countries over the last few de cades, and identifying better ways of treating this cancer is paramount. Although surgery of CRC remains the best treatment, adjuvant chemotherapy and radio therapy are also very important and beneficial treat ments for patients. After surgery, chemotherapy and radiotherapy is used to target small cancerous tis sues that may be missed during surgery and help to prevent cancer recurrence. Aurora kinases are the most important serine threonine protein kinases which regulate the function of centrosomes, spin dles, and kinetochores for proper mitotic progression. Aurora A overexpression has been observed in vari ous cancers including colorectal cancers. Baba et.