Short hairpin RNA- mediated gene knockdown of FOXM1 inhibits the proliferation and metastasis of human colon cancer cells through reversal of epithelial-to-mesenchymal transformation.
BACKGROUND
The Forkhead box M1 (FOXM1) is an oncogenic transcription factor and plays a significant role in cell EMT, proliferation, metastasis in a multitude of human solid tumors including colorectal cancer (CRC). However, the underlying molecular mechanisms by which FoxM1 contributes to epithelial-to-mesenchymal (EMT) and metastasis have not been fully elucidated in CRC.


METHODS
In our study, we investigated FOXM1 protein expression in 87 CRC tissue specimens, invasive lymph nodes and adjacent paired normal colorectal tissues by immunohistochemical analysis. Then we transfected FOXM1 specific shRNA into SW620 cells to examine effect of FOXM1 on proliferation, colony formation, migration and invasion in vitro. Western blotting and real-time PCR were used to detect the protein and mRNA expression of FOXM1 and EMT-related markers.


RESULTS
FOXM1 was overexpressed in CRC tissues, invasive lymph nodes and CRC cell lines. FoxM1 overexpression was significantly associated with lymph node metastasis (P < 0.001), and tumor recurrence (P < 0.001). Moreover, downregulation of FOXM1 in SW620 cells by shRNA approach inhibited cell growth, clonogenicity, migration and invasion in vitro. In addition, decreased FOXM1 expression in SW620 cells reversed the acquisition of EMT phenotype by up-regulating E-cadherin, as well as reduction Vimentin and Snail expressions at protein and mRNA levels.


CONCLUSIONS
FOXM1 may regulate CRC cells metastasis through EMT program and FOXM1 may be a potential target for treatment of CRC.
Department of General Surgery, The First Affiliated Hospital of Soochow University, 215006, Suzhou, Jiangsu Province, China. ykk0821010030@163.com.
KanKan
K
Yang
Department of General Surgery, The First Affiliated Hospital of Soochow University, 215006, Suzhou, Jiangsu Province, China. jianglinhuaaaa@163.com.
LinHua
L
Jiang
Department of Laparoscopic Surgery, The First Affiliated Hospital of Soochow University, 215006, Suzhou, Jiangsu Province, China. huyoulove@163.com.
You
Y
Hu
Department of General Surgery, The First Affiliated Hospital of Soochow University, 215006, Suzhou, Jiangsu Province, China. yujing0509@163.com.
Jing
J
Yu
Department of General Surgery, The First Affiliated Hospital of Soochow University, 215006, Suzhou, Jiangsu Province, China. suzhouwheat2@163.com.
HenFeng
H
Chen
Department of General Surgery, The First Affiliated Hospital of Soochow University, 215006, Suzhou, Jiangsu Province, China. yaoyizhou2014@163.com.
YiZhou
Y
Yao
Department of General Surgery, The First Affiliated Hospital of Soochow University, 215006, Suzhou, Jiangsu Province, China. professorzxg@hotmail.com.
XinGuo
X
Zhu
D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics*; D047368:Tumor Burden; D015854:Up-Regulation
C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering