title: Targeting miR-21 enhances the sensitivity of human colon cancer HT-29 cells to chemoradiotherapy in vitro.
abstract: 5-Fluorouracil (5-FU) is a classic chemotherapeutic drug that has been widely used for colorectal cancer treatment, but colorectal cancer cells are often resistant to primary or acquired 5-FU therapy. Several studies have shown that miR-21 is significantly elevated in colorectal cancer. This suggests that this miRNA might play a role in this resistance. In this study, we investigated this possibility and the possible mechanism underlying this role. We showed that forced expression of miR-21 significantly inhibited apoptosis, enhanced cell proliferation, invasion, and colony formation ability, promoted G1/S cell cycle transition and increased the resistance of tumor cells to 5-FU and X radiation in HT-29 colon cancer cells. Furthermore, knockdown of miR-21 reversed these effects on HT-29 cells and increased the sensitivity of HT-29/5-FU to 5-FU chemotherapy. Finally, we showed that miR-21 targeted the human mutS homolog2 (hMSH2), and indirectly regulated the expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD). These results demonstrate that miR-21 may play an important role in the 5-FU resistance of colon cancer cells.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.
authors.forename: Wan
authors.initials: W
authors.lastname: Lei
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.
authors.forename: Jian-Chun
authors.initials: JC
authors.lastname: Fu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.
authors.forename: Jun-He
authors.initials: JH
authors.lastname: Li
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, PR China. Electronic address: jpxiong@medmail.com.cn.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Xiong
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D001483:Base Sequence; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D059248:Chemoradiotherapy; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009361:Neoplasm Invasiveness; D013939:Thymidine Phosphorylase / Q000235:genetics / Q000378:metabolism; D014410:Tumor Stem Cell Assay
chemical_list: D020413:3' Untranslated Regions; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D042943:Dihydrouracil Dehydrogenase (NADP); D013939:Thymidine Phosphorylase; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein; D005472:Fluorouracil
keywords: 5-FU; CRC; Chemo-resistance; DPD; HT-29; MMR; NC; TP; TS; UTR; colorectal cancer; dihydropyrimidine dehydrogenase; hMSH2; miR-21; mismatch repair system; nonsense control; qRT-PCR; quantitative real time polymerase chain reaction; thymidine phosphorylase; thymidylate synthase; untranslated regions