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Updated: Dec 13, 2025

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
The inhibition of microRNA-326 by SP1/HDAC1 contributes to proliferation and metastasis of osteosarcoma through
Jiang-Hu Huang1,2, Yang Xu1,2, Fei-Yue Lin1,2
1Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Abstract:
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.
Insights
MicroRNA-326 (miR-326) suppresses osteosarcoma (OS) growth and metastasis. SP1/HDAC1 complex inhibits miR-326, promoting OS cell proliferation and spread.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Osteosarcoma (OS) is a bone cancer with limited treatment options for metastatic disease.
- Identifying novel therapeutic targets for metastatic OS is crucial.
Purpose of the Study:
- To investigate the role of MicroRNA-326 (miR-326) in osteosarcoma proliferation and metastasis.
- To elucidate the regulatory mechanism of miR-326 in OS.
Main Methods:
- Microarray assay to identify SP1-influenced miRNAs.
- Cellular assays (MTT, EdU, wound-healing, invasion) for proliferation and invasion.
- In vivo nude mice model for metastasis detection.
- Chromatin immunoprecipitation (ChIP) and DNA-binding assays to study SP1/HDAC1 regulation of miR-326.
Main Results:
- Human OS tissues exhibit low miR-326 and high SP1/HDAC1 expression.
- SP1 recruits HDAC1 to the miR-326 promoter, inhibiting its transcription via histone deacetylation.
- miR-326 deficiency promotes OS cell proliferation, invasion, and metastasis in vivo by activating the SMO/Hedgehog pathway.
Conclusions:
- SP1/HDAC1 complex transcriptionally inhibits miR-326 in OS.
- miR-326 deficiency drives OS proliferation and metastasis through SMO/Hedgehog pathway activation.
- Targeting the SP1/HDAC1/miR-326 axis may offer a therapeutic strategy for metastatic OS.
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