title: Suppression of nucleosome-binding protein 1 by miR-326 impedes cell proliferation and invasion in non-small cell lung cancer cells.
abstract: Emerging studies have proposed microRNAs (miRNAs) as novel therapeutic tools for cancer therapy. Nucleosome-binding protein 1 (NSBP1) has been suggested as an oncogene in various types of human cancers. The present study aimed to identify a novel miRNA that could directly target and negatively modulate NSBP1 expression. We found that NSBP1 was highly expressed in non‑small cell lung cancer (NSCLC) cells, and knockdown of NSBP1 by NSBP1 small interfering RNA (siRNA) significantly suppressed NSCLC cell proliferation and invasion. Bioinformatics analysis revealed that miR‑326 had a putative binding site within the 3'‑untranslated region of NSBP1. Their substantial relationship was further verified by dual‑luciferase reporter assay, real‑time quantitative polymerase chain reaction and western blot analysis. Overexpression of miR‑326 significantly inhibited NSCLC cell proliferation and invasion, which mimicked the effect of NSBP1 siRNA. Furthermore, suppression of NSBP1 by NSBP1 siRNA or miR‑326 overexpression remarkably repressed the expression of cyclin B1 and matrix metalloproteinase 9 (MMP9), which are associated with cancer cell proliferation and invasion. Moreover, overexpression of NSBP1 obviously abolished the inhibitory effect of miR‑326 on cyclin B1 and MMP9 expression. In addition, an inverse correlation between miR‑326 and NSBP1 expression levels was found in NSCLC clinical specimens. Our study demonstrated a direct target relationship between NSBP1 and miR‑326 through which miR‑326 inhibited cell proliferation and invasion of NSCLC cells. Thus, miR‑326‑NSBP1 is a promising candidate target for developing novel anticancer therapeutics for NSCLC.
authors.affiliation: Department of Respiration Medicine, The Xi'an Central Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Dongfan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Respiration Medicine, The Xi'an Central Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Xusheng
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Respiration Medicine, The Xi'an Central Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: An
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division; D002460:Cell Line; D045744:Cell Line, Tumor; D056744:Cyclin B1 / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D057809:HEK293 Cells; D024001:HMGN Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D006801:Humans; D015603:Keratinocytes; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D034622:RNA Interference; D012334:RNA, Neoplasm / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology
chemical_list: D020413:3' Untranslated Regions; C534699:CCNB1 protein, human; D056744:Cyclin B1; D024001:HMGN Proteins; C429289:HMGN5 protein, human; C545322:MIRN326 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D015534:Trans-Activators; D020780:Matrix Metalloproteinase 9