Kruppel-like factor 9 inhibits growth and metastasis of cholangiocarcinoma cells by targeted regulation of metallothionein 1 M transcription

Abstract

This study is to investigate the effect of Kruppel-like factor 9 (KLF9) on the occurrence and progression of cholangiocarcinoma (CCA) and its underlying mechanism. After the CCA cells were transfected with OE-KLF9 and/or sh-metallothionein 1 M (sh-MT1M), KLF9 and MT1M expression levels were measured. Likewise, the biological characteristics of CCA cells were measured, followed by detections of caspase3 activity and epithelial mesenchymal transition (EMT)-related protein. Furthermore, the binding site of KLF9 and MT1M was predicted and verified. An in vivo model of CCA in nude mice was established where tumor volume and weight were recorded, in addition to tumor metastasis in the liver. The expression of KLF9 and MT1M in the CCA cells was remarkably lower. CCA cells overexpressing KLF9 showed repressed abilities to proliferate, invade, and migrate, and strengthened cell apoptosis. KLF9 inhibited EMT, growth, and migration of CCA cells by modulating MT1M transcription. Additionally, KLF9 facilitated MT1M expression in vivo and improve the progression of CCA in nude mice. KLF9 acted as a transcription factor of MT1M to promote its transcription level, thereby affecting the growth and migration of CCA cells, and ultimately improving the occurrence and development of CCA.