title: MicroRNA-143 replenishment re-sensitizes colorectal cancer cells harboring mutant, but not wild-type, KRAS to paclitaxel treatment.
abstract: Colorectal cancer (CRC) global incidence is one of the highest among cancers. The KRAS gene has been shown as a robust biomarker for poor prognosis and drug resistance. MicroRNA-143 (miR-143) and let-7 are families of tumor suppressor microRNAs that are often downregulated in CRC, especially with coexistent KRAS mutations. In order to evaluate if miR-143 and/or let-7b replenishment would re-sensitize CRC cells to paclitaxel treatment, we investigated in effect of miR-143 and let-7b replenishments on sensitivity to paclitaxel treatment in KRAS mutant LoVo and wild-type SW48 CRC cell lines. Our results showed that miR-143, but not let-7b, increased sensitization of KRAS mutant tumor cells to paclitaxel. Furthermore, transfection of miR-143, but not let-7b, mimic negatively regulated the expression of mutant but not wild-type KRAS. Combination of miR-143 mimic and paclitaxel induced the onset of apoptosis, and reverted in vitro metastatic properties (migration and invasion) in KRAS mutant tumor cells. MiR-143 thus can be used as a chemosensitizer for the treatment of KRAS mutant tumors and warrants further investigations in in vitro and pre-clinical in vivo models.
authors.affiliation: Department of General Surgery, China Japan Union Hospital of Jilin University, 829Xin'min Road, Chaoyang District, Changchun, 130012, China.
authors.forename: Bing-Yuan
authors.initials: BY
authors.lastname: Fei
authors.affiliation: Medical Record Department, China Japan Union Hospital of Jilin University, Changchun, 130021, China.
authors.forename: Xiu-Ying
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Department of General Surgery, China Japan Union Hospital of Jilin University, 829Xin'min Road, Chaoyang District, Changchun, 130012, China. xdf_cjuh@126.com.
authors.forename: Xue-Dong
authors.initials: XD
authors.lastname: Fang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D011905:Genes, ras; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis; D017239:Paclitaxel / Q000494:pharmacology*; D012313:RNA / Q000235:genetics; D014162:Transfection
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C542359:MIRN143 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; C039919:RNA, recombinant; C487931:mirnlet7 microRNA, human; D012313:RNA; D015689:Oncogene Protein p21(ras); D017239:Paclitaxel
keywords: Colorectal cancer; KRAS; let-7b; miR-143