title: microRNA-200c downregulates XIAP expression to suppress proliferation and promote apoptosis of triple-negative breast cancer cells.
abstract: Despite advances in the understanding of breast cancer, patients most commonly have a poor prognosis, particularly those with triple negative breast cancer (TNBC). microRNAs (miRNAs) are endogenous non‑coding small RNAs, and their aberrant expression is linked to numerous malignancies. In the present study, the expression levels of miR‑200c in patients with TNBC were analyzed and it was identified that miR‑200c was downregulated in TNBC samples, compared with that in normal adjacent tissues. miR‑200c was overexpressed in the TNBC cell line MDA‑MB‑231 and its functions were studied in vitro and in vivo. An in vitro study revealed that the overexpression of miR‑200c inhibited MDA‑MB‑231 cell proliferation and resulted in the induction of apoptosis. The in vivo data indicated that the overexpression of miR‑200c significantly inhibited tumor growth and increased the rate of apoptosis. Target prediction revealed that the X‑linked inhibitor of apoptosis (XIAP) had putative complementary sequences to miR‑200c, which was confirmed by a dual luciferase reporter assay. Western blot analysis further demonstrated that the expression of XIAP was markedly reduced and that caspase‑3 was highly activated by the overexpression of miR‑200c. These findings suggested that miR‑200c may function as a tumor suppressor gene in TNBC, at least partly via directly targeting XIAP, and may therefore act as a potential therapeutic target in the development of novel treatment strategies for TNBC.
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Breast and Thyroid Surgery, Huai'an First People's Hospital, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Xuedong
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Cardiology, Huai'an First People's Hospital, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yu
authors.affiliation: Department of Pathology, Huai'an First People's Hospital, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Su'an
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Breast and Thyroid Surgery, Huai'an First People's Hospital, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Zhen
authors.affiliation: Department of Breast and Thyroid Surgery, Huai'an First People's Hospital, Huai'an, Jiangsu 223300, P.R. China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Shui
authors.initials: S
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment; D014183:Transplantation, Heterologous; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D053148:Caspase 3