KRT19 promotes colorectal cancer progression through mTOR pathway via SIRT4.

Abstract

Keratin19 (KRT19) is the smallest type I KRT protein which is a member of the keratin family. KRT19 has been reported as a diagnostic marker in several cancers, such as lung, breast and pancreatic cancer. However, the diagnostic value and potential role of KRT19 in colorectal cancer (CRC) remain to be explored. Our study confirmed the KRT19 expression pattern in CRC through publicly database and in CRC patient tissues with immunohistochemistry (IHC) and Western blot. Then, we carried out a series of malignant phenotype assays like colony formation assay, transwell migration and invasion experiments to definite the role of KRT19 on CRC cells proliferation, migration and invasion. Co-immunoprecipitation (co-IP) and Western blot were utilized to clarify the underlying molecular mechanisms of KRT19 in CRC. The data from GEPIA and CRC specimens displayed that KRT19 expression was increased and correlated with a poor clinical outcome. Our in vitro experiments confirmed that KRT19 promoted the proliferation, migration and invasion of CRC cells. Moreover, co-IP verified the interaction between KRT19 and SIRT4. KRT19 also activated the mTOR pathway which was illustrated by Western blot. Our research provides that KRT19 may be served as a diagnostic marker for CRC, and KRT19 promotes CRC progression through mTOR pathway by interacting with SIRT4.