title: Knockdown of lncRNA-ATB suppresses autocrine secretion of TGF-β2 by targeting ZNF217 via miR-200c in keloid fibroblasts.
abstract: Abnormally high activation of transforming growth factor-β (TGF-β) signaling has been demonstrated to be involved in the initiation and progression of keloids. However, the functional role of long non-coding RNA (lncRNA)-activated by TGF-β (lncRNA-ATB) in keloids has not been documented. Here we investigated the role of lncRNA-ATB in the autocrine secretion of TGF-β in keloid fibroblasts (KFs) and explored the underlying molecular mechanism. Using immunohistochemistry and quantitative RT-PCR analysis, we showed that lncRNA-ATB and ZNF217, a transcriptional activator of TGF-β, were overexpressed and miR-200c, which targets ZNF217, was under-expressed in keloid tissue and keloid fibroblasts. Through gain- and loss-of-function studies, we demonstrated that knockdown of lncRNA-ATB decreased autocrine secretion of TGF-β2 and ZNF217 expression but upregulated expression of miR-200c in KFs. Stable downregulation of ZNF217 expression decreased the autocrine secretion of TGF-β2. miR-200c was endogenously associated with lncRNA-ATB, and inhibition of miR-200c overcame the decrease in ZNF217 expression in KFs. Taken together, these findings indicate that lncRNA-ATB governs the autocrine secretion of TGF-β2 in KFs, at least in part, by downregulating the expression level of ZNF217 via miR-200c, suggesting a signaling axis consisting of lncRNA-ATB/miR-200c/ZNF217/TGF-β2. These findings may provide potential biomarkers and targets for novel diagnostic and therapeutic approaches for keloids.
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, People's Republic of China.
authors.forename: Hua-Yu
authors.initials: HY
authors.lastname: Zhu
authors.affiliation: Department of Hematology, Urumqi General Hospital of Chinese People's Liberation Army, Urumqi, 830000, Xinjiang, People's Republic of China.
authors.forename: Wen-Dong
authors.initials: WD
authors.lastname: Bai
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, People's Republic of China.|Center of Military Burns and Plastic Surgery, Lanzhou General Hospital of Lanzhou Military Command of Chinese PLA, Lanzhou, 730050, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, People's Republic of China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, People's Republic of China.
authors.forename: Jia-Qi
authors.initials: JQ
authors.lastname: Liu
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, People's Republic of China.
authors.forename: Xue-Kang
authors.initials: XK
authors.lastname: Yang
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, People's Republic of China.
authors.forename: Shi-Chao
authors.initials: SC
authors.lastname: Han
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, People's Republic of China.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Gao
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, People's Republic of China.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Wang
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, People's Republic of China.
authors.forename: Da-Hai
authors.initials: DH
authors.lastname: Hu
mesh_terms: D015415:Biomarkers; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D007627:Keloid / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D053781:Transforming Growth Factor beta2 / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D015534:Trans-Activators; D053781:Transforming Growth Factor beta2; C113698:ZNF217 protein, human