title: Overexpression of microRNA-122 re-sensitizes 5-FU-resistant colon cancer cells to 5-FU through the inhibition of PKM2 in vitro and in vivo.
abstract: 5-Fluorouracil (5-FU) is one of the most commonly used anticancer drugs in the treatment of colon cancer. However, acquired chemoresistance is becoming one of the major challenges for patients with advanced stages of colon cancer. Currently, the mechanisms underlying cancer cell resistance to 5-FU are not fully understood. MicroRNAs (miRNA) have been suggested to play important roles in tumorigenesis and drug resistance in colon cancer. In this study, we generated 5-FU-resistant colon cancer cell lines from which we found that miR-122 was downregulated in 5-FU-resistant cells compared with sensitive cells. Meanwhile, the glucose metabolism is significantly upregulated in 5-FU-resistant cells. We report that PKM2 is a direct target of miR-122 in colon cancer cell. Importantly, overexpression of miR-122 in 5-FU-resistant cells resensitizes 5-FU resistance through the inhibition of PKM2 both in vitro and in vivo. In summary, these findings reveal that the dysregulated glucose metabolism contributes to 5-FU resistance, and glycolysis inhibition by miR-122 might be a promising therapeutic strategy to overcome 5-FU resistance.
authors.affiliation: Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jinxia
authors.initials: J
authors.lastname: He
authors.forename: Ganfeng
authors.initials: G
authors.lastname: Xie
authors.forename: Jingtao
authors.initials: J
authors.lastname: Tong
authors.forename: Yonghai
authors.initials: Y
authors.lastname: Peng
authors.forename: Haihui
authors.initials: H
authors.lastname: Huang
authors.forename: Jianjun
authors.initials: J
authors.lastname: Li
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Houjie
authors.initials: H
authors.lastname: Liang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005472:Fluorouracil / Q000494:pharmacology*; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D013963:Thyroid Hormones / Q000235:genetics*; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D005472:Fluorouracil; D005947:Glucose; D008565:Membrane Proteins; D035683:MicroRNAs; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C531907:MIRN122 microRNA, human