MicroRNA-21-mediated regulation of Sprouty2 protein expression enhances the cytotoxic effect of 5-fluorouracil and metformin in colon cancer cells.
Sprouty2 (Spry2) was identified recently as a tumor suppressor gene in cancer             cells which inhibits the activation of receptor tyrosine kinases (RTKs). The present             study explored the effect of Spry2 in colon cancer cells in order to assess its             potential use in the treatment of colon cancer. Expression of Spry2 inhibited             the growth of a colon cancer cell line, HCT116, and induced sensitization to fluorouracil             (5-FU) and metformin. Spry2 promoted apoptosis of cancer cells in association             with activation of the phosphatase and tensin homolog deleted on chromosome 10             (PTEN) pathway and the blockade of Ras-Raf-Erk signaling. Treatment of Spry2-HCT116             cells with metformin resulted in a more prominent effect on the inhibition of             cell migration. Inhibition of microRNA-21 (mir‑21) induced upregulation of Spry2             and PTEN which underscores the importance of mir-21 in Spry2-associated tumorigenesis             of the colon. These results point toward a potential strategy for colon cancer             treatment worthy of further investigation.
Division of Hematology and Oncology, Department of Internal Medicine,                     Chi-Mei Medical Center, Yong Kang, Tainan 71004, Taiwan, R.O.C.
Yin-Hsun
YH
Feng
Chao-Liang
CL
Wu
Ai-Li
AL
Shiau
Jenq-Chang
JC
Lee
Jan-Gowth
JG
Chang
Pei-Jung
PJ
Lu
Chao-Ling
CL
Tung
Li-Yia
LY
Feng
Wen-Tsung
WT
Huang
Chao-Jung
CJ
Tsao
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002465:Cell Movement; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins; D008687:Metformin / Q000494:pharmacology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D000964:Antimetabolites, Antineoplastic; D007004:Hypoglycemic Agents; D047908:Intracellular Signaling Peptides and Proteins; C524940:MIRN21 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; C485561:SPRY2 protein, human; D008687:Metformin; D051059:PTEN Phosphohydrolase; D005472:Fluorouracil