title: miR‑34c‑3p acts as a tumor suppressor gene in osteosarcoma by targeting MARCKS.
abstract: Previous studies have demonstrated that microRNA (miR)‑34c‑3p is important in human cancer progression. However, the function of miR‑34c‑3p in osteosarcoma (OS) remains to be elucidated. In the present study, miR‑34c‑3p level was measured by reverse transcription‑quantitative polymerase chain reaction in OS tissues and the associated prognostic value for overall survival was determined. The function of miR‑34c‑3p was examined in vitro and in vivo. A luciferase reporter assay was used to identify the targets of miR‑34c‑3p. The results of the present study revealed that miR‑34c‑3p was downregulated in OS tissues and cell lines, and decreased levels of miR‑34c‑3p were associated with a high mortality rate in patients with OS. Furthermore, restoration of miR‑34c‑3p expression reduced cell growth in vitro and suppressed tumorigenesis in vivo. Conversely, inhibition of miR‑34c‑3p stimulated OS cell growth in vitro and in vivo. Myristoylated alanine‑rich protein kinase C substrate (MARCKS) was identified as a direct target of miR‑34c‑3p and its overexpression partly reversed the suppressive effects of miR‑34c‑3p. Furthermore, MARCKS was revealed to be upregulated and inversely correlated with miR‑34c‑3p levels in OS tissues. These data suggested that miR‑34c‑3p acts as a tumor suppressor via regulation of MARCKS expression in OS progression and miR‑34c‑3p may be a promising therapeutic target for this type of cancer.
authors.affiliation: Department of Foot and Ankle Surgery, Xi'an Honghui Hospital, Xi'an, Shanxi 710054, P.R. China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Surgery, Xi'an Honghui Hospital, Xi'an, Shanxi 710054, P.R. China.
authors.forename: Pengxiao
authors.initials: P
authors.lastname: Su
authors.affiliation: Department of Articular Orthopedics, Xi'an Honghui Hospital, Xi'an, Shanxi 710054, P.R. China.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Zhi
authors.affiliation: Department of Foot and Ankle Surgery, Xi'an Honghui Hospital, Xi'an, Shanxi 710054, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics* / Q000401:mortality; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D012516:Osteosarcoma / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D034622:RNA Interference; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D047908:Intracellular Signaling Peptides and Proteins; C000619710:MARCKS protein, human; C522425:MIRN34 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D000076250:Myristoylated Alanine-Rich C Kinase Substrate