title: MicroRNA-499-5p promotes cellular invasion and tumor metastasis in colorectal cancer by targeting FOXO4 and PDCD4.
abstract: MicroRNAs (miRNAs) regulate tumor progression and invasion via direct interaction with target messenger RNAs (mRNAs). We defined miRNAs involved in cancer metastasis (metastamirs) using an established in vitro colorectal cancer (CRC) model of minimally metastatic cells (SW480 line) from a colon adenocarcinoma primary lesion and highly metastatic cells (SW620 line) from a metastatic lymph node from the same patient 1 year later. We used microarray analysis to identify miRNAs differentially expressed in SW480 and SW620 cells, focusing on miR-499-5p as a novel candidate prometastatic miRNA whose functions in cancer had not been studied. We confirmed increased miR-499-5p levels in highly invasive CRC cell lines and lymph node-positive CRC specimens. Furthermore, enhancing the expression of miR-499-5p promoted CRC cell migration and invasion in vitro and lung and liver metastasis in vivo, while silencing its expression resulted in reduced migration and invasion. Additionally, we identified FOXO4 and PDCD4 as direct and functional targets of miR-499-5p. Collectively, these findings suggested that miR-499-5p promoted metastasis of CRC cells and may be useful as a new potential therapeutic target for CRC.
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, 17 Changle Western Road, Xi'an, Shaanxi Province, 710032, People's Republic of China.
authors.forename: Xiangqiang
authors.initials: X
authors.lastname: Liu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Na
authors.initials: N
authors.lastname: Chai
authors.forename: Shanhong
authors.initials: S
authors.lastname: Tang
authors.forename: Jiang
authors.initials: J
authors.lastname: Jin
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.forename: Yongzhan
authors.initials: Y
authors.lastname: Nie
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Kaichun
authors.initials: K
authors.lastname: Wu
authors.forename: Haifeng
authors.initials: H
authors.lastname: Jin
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001483:Base Sequence; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D017931:DNA Primers; D005260:Female; D051858:Forkhead Transcription Factors; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D017931:DNA Primers; C108803:FOXO4 protein, human; D051858:Forkhead Transcription Factors; C548683:MIRN499 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; D014157:Transcription Factors