miR-221 Promotes Epithelial-Mesenchymal Transition through Targeting PTEN and Forms a Positive Feedback Loop with β-catenin/c-Jun Signaling Pathway in Extra-Hepatic Cholangiocarcinoma.
Extrahepatic cholangiocarcinoma (EHCC) is a refractory malignancy with poor prognosis due to its early invasion, metastasis and recurrence after operation. Therefore, understanding the mechanisms of invasion and metastasis is the key to the development of new and effective therapeutic strategies for EHCC. In the present study we demonstrated that miR-221 promoted EHCC invasion and metastasis through targeting PTEN and formed a positive feedback loop with β-catenin/c-Jun signaling pathway. We found miR-221 was upregulated in EHCC specimens and CC cell lines. Moreover, miR-221 was found strongly associated with the metastasis and prognosis of EHCC patients. The expression of PTEN was downregulated in EHCC patients and CC cell lines, and was further demonstrated as one of the downstream targets of miR-221. In addition, our data indicated that β-catenin activated miR-221 through c-jun, while miR-221 enhanced β-catenin signaling induced-epithelial-mesenchymal transition (EMT) by targeting PTEN, hence forming a positive feedback loop in EHCC cell lines. In conclusion, our results suggested that miR-221 promotes EMT through targeting PTEN and forms a positive feedback loop with β-catenin/c-Jun signaling pathway in EHCC.
Department of General Surgery, the First Affiliated Hospital of JILIN University, Changchun, 130021, P.R. China.
Jianguo
J
Li
Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, P.R. China.
Lei
L
Yao
Department of General Surgery, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, P.R. China.
Guodong
G
Li
Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, P.R. China.
Donglai
D
Ma
Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, P.R. China.
Chen
C
Sun
Heilongjiang Nursing College, Harbin, 150086, P.R. China.
Shuang
S
Gao
Department of General Surgery, the First Affiliated Hospital of JILIN University, Changchun, 130021, P.R. China.
Ping
P
Zhang
Department of General Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, P.R. China.
Feng
F
Gao
D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D006801:Humans; D008099:Liver / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; D051176:beta Catenin; C525709:MIR221, human; C494929:PTEN protein, human