title: Long non-coding RNA BACE1-AS is a novel target for anisomycin-mediated suppression of ovarian cancer stem cell proliferation and invasion.
abstract: Human ovarian cancer stem cells (OCSCs) are one of the main factors affecting ovarian cancer cell metastasis, recurrence, prognosis and tolerance to chemotherapy drugs. However, the mechanisms of OCSC proliferation and invasion are not clear. Recent studies suggest that anisomycin can inhibit the proliferative and invasive ability of various tumor cells by increasing the production of the toxic amyloid β (Aβ1-42) peptides from the amyloid precursor protein (APP). We explored whether anisomycin could also suppress human OCSC proliferation and invasion. The CD44+/CD117+ OCSCs were enriched from human clinical ovarian tumor tissues. OCSCs treated with anisomycin showed reduced proliferation compared to controls. Moreover, anisomycin significantly suppressed the invasive capacity of OCSCs in vitro, as indicated by cell migration assays. The mRNA expression levels of long non-coding RNA (lncRNA) β-site APP cleaving enzyme 1 antisense strand (BACE1-AS) were significantly increased in anisomycin-treated OCSCs compared to controls. In addition, mRNA and protein levels of BACE1 and Aβ1-42 were increased in anisomycin-treated OCSCs compared to controls. We confirmed that anisomycin suppressed the growth of xenograft tumors formed by OCSCs in vivo. Finally, when expression of lncRNA BACE1-AS was silenced using siRNA, BACE1 expression was downregulated and the antiproliferative and anti-invasive effects of anisomycin were reduced. Overall, we identified lncRNA BACE1-AS as a novel target for anisomycin. Elevation of lncRNA BACE1-AS expression is a potential mechanism for suppressing human OCSC proliferation and invasion.
authors.affiliation: Gongli Hospital Affiliated to The Second Military Medical University in Pudong New Area of Shanghai City, Shanghai 200135, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Gongli Hospital Affiliated to The Second Military Medical University in Pudong New Area of Shanghai City, Shanghai 200135, P.R. China.
authors.forename: Xinghui
authors.initials: X
authors.lastname: Liu
authors.affiliation: Gongli Hospital Affiliated to The Second Military Medical University in Pudong New Area of Shanghai City, Shanghai 200135, P.R. China.
authors.forename: Limin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Gongli Hospital Affiliated to The Second Military Medical University in Pudong New Area of Shanghai City, Shanghai 200135, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China.
authors.forename: Suwei
authors.initials: S
authors.lastname: Wang
authors.affiliation: Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Li
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, P.R. China.
authors.forename: Yongyi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Shanghai Geriatric Institute of Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, P.R. China.
authors.forename: Te
authors.initials: T
authors.lastname: Liu
mesh_terms: D000328:Adult; D000818:Animals; D000841:Anisomycin / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: C561565:BACE1-AS long non-coding RNA, human; D062085:RNA, Long Noncoding; D000841:Anisomycin