The inhibition of microRNA‐326 by SP1/HDAC1 contributes to proliferation and metastasis of osteosarcoma through promoting SMO expression

• Published in: Journal of cellular and molecular medicine Vol. 24; no. 18; pp. 10876 - 10888
• Main Authors: Huang, Jiang‐Hu, Xu, Yang, Lin, Fei‐Yue
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.09.2020; John Wiley and Sons Inc
• Subjects: Adolescent; Adult; Animals; Binding sites; Bone cancer; Bone Neoplasms - genetics; Bone Neoplasms - pathology; Cell Division - drug effects; Cell growth; Cell Line, Tumor; Cell Movement - drug effects; Cell proliferation; Deacetylation; Deoxyribonucleic acid; DNA; DNA methylation; DNA microarrays; Epigenetics; Female; Gene expression; Gene Knockdown Techniques; Histone deacetylase; Histone Deacetylase 1 - antagonists & inhibitors; Histone Deacetylase 1 - genetics; Histone Deacetylase 1 - physiology; Humans; Male; Manufacturers; Matrix Metalloproteinase 9 - physiology; Metastases; Metastasis; Mice; Mice, Nude; MicroRNAs; MicroRNAs - antagonists & inhibitors; MicroRNAs - biosynthesis; MicroRNAs - genetics; miRNA; miR‐326; Neoplasm Metastasis - genetics; Neoplasm Metastasis - physiopathology; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Neoplasm Proteins - physiology; Original; Osteosarcoma; Osteosarcoma - genetics; Osteosarcoma - pathology; Osteosarcoma - secondary; RNA Interference; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; RNA, Neoplasm - antagonists & inhibitors; RNA, Neoplasm - biosynthesis; RNA, Neoplasm - genetics; RNA, Small Interfering - genetics; RNA, Small Interfering - pharmacology; Sarcoma; Smoothened Receptor - biosynthesis; Smoothened Receptor - genetics; Sp1; Sp1 protein; Sp1 Transcription Factor - antagonists & inhibitors; Sp1 Transcription Factor - genetics; Sp1 Transcription Factor - physiology; Transcription; Transcription factors; Wound healing; Xenograft Model Antitumor Assays; Young Adult; Zinc Finger Protein GLI1 - physiology; China; miR-326; Sp1; metastasis; histone deacetylase; osteosarcoma
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.15716

Osteosarcoma (OS) is a malignant bone cancer lacking of effective treatment target when the metastasis occurred. This study investigated the implication of MicroRNA‐326 in OS proliferation and metastasis to provide the clue for the treatment of metastatic OS. This study knocked down SP1 in MG63 and 143B cells and then performed Microarray assay to find the expression of miRNAs that were influenced by SP1. MTT, EdU, wound‐healing and cell invasion assays were performed to evaluated cell proliferation and invasion. OS metastasis to lung was detected in a nude mice model. ChIP assay and DAPA were applied to determine the regulatory effect of SP1 and histone deacetylase 1 (HDAC) complex on miR‐326 expression. Human OS tissues showed lowly expressed miR‐326 but highly expressed Sp1 and HDAC. Sp1 recruited HDAC1 to miR‐326 gene promoter, which caused the histone deacetylation and subsequent transcriptional inhibition of miR‐326 gene. miR‐326 deficiency induced the stimulation of SMO/Hedgehog pathway and promoted the proliferation and invasion of 143B and MG63 cells as well as the growth and metastasis in nude mice. SP1/HDAC1 caused the transcriptional inhibition of miR‐326 gene by promoting histone deacetylation; miR‐326 deficiency conversely stimulated SMO/Hedgehog pathway that was responsible for the proliferation and metastasis of OS.