title: Blockage of TGFβ-SMAD2 by demethylation-activated miR-148a is involved in caffeic acid-induced inhibition of cancer stem cell-like properties in vitro and in vivo.
abstract: Current standard practices for treatment of cancers are less than satisfactory because of recurrence mediated by cancer stem cells (CSCs). Caffeic acid (CaA) is a novel anti-tumor agent that inhibits proliferation, migration, and invasion in human cancer cells. However, little is known about the functions of CaA in regulating CSCs-like properties and the potential molecular mechanisms. Here, we found that CaA attenuated the CSCs-like properties by the microRNA-148a (miR-148a)-mediated inhibition of transforming growth factor beta (TGFβ)-SMAD2 signaling pathway both in vitro and in vivo. CaA enhanced the expression of miR-148a by inducing DNA methylation. MiR-148a, which targeted the SMAD2-3'UTR, decreased the expression of SMAD2. Knockdown of miR-148a abolished the CaA-induced inhibition of TGFβ-SMAD2 signal pathway and the CSCs-like properties. Our study found a novel mechanism that CaA inhibits the CSCs-like properties via miR-148a-mediated inhibition of TGFβ-SMAD2 signaling pathway, which may help to identify a new approach for the treatment of human cancers.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Department of Hygiene Analysis and Detection, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Hygiene Analysis and Detection, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Hygiene Analysis and Detection, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Hygiene Analysis and Detection, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Xingxing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Mu
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Hygiene Analysis and Detection, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
keywords: CSCs, cancer stem cells; CaA, 3,4-dihydroxycinnamic acid; Caffeic acid; Cancer stem cells-like properties; DNA methylation; DNMT, DNA methyltransferases; HCC, hepatocellular carcinoma; SAM, S-adenosylmethionine; TGFβ, transforming growth factor beta; TNBC, triple-negative breast cancer; Transforming growth factor beta-SMAD2 signal pathway; miR-148a, microRNA-148a; microRNA-148a; qMSP, quantitative methylation-specific polymerase chain reaction