LncRNA ODRUL Contributes to Osteosarcoma Progression through the miR-3182/MMP2 Axis.

Recent findings have shown that lncRNA dysregulation is involved in many cancers, including osteosarcoma (OS). In a previous study, we reported a novel lncRNA, ODRUL, that could promote doxorubicin resistance in OS. We now report the function and underlying mechanism of ODRUL in regulating OS progression. We show that ODRUL is upregulated in OS tissues and cell lines and correlates with poor prognosis. ODRUL knockdown significantly inhibits OS cell proliferation, migration, invasion, and tumor growth in vitro and in vivo by decreasing matrix metalloproteinase (MMP) expression. A microarray screen combined with online database analysis showed that miR-3182 is upregulated and MMP2 is downregulated in sh-ODRUL-expressing MG63 cells and that miR-3182 harbors potential binding sites for ODRUL and the 3' UTR of MMP2 mRNA. In addition, miR-3182 expression and function are inversely correlated with ODRUL expression in vitro and in vivo. A luciferase reporter assay demonstrated that ODRUL could directly interact with miR-3182 and upregulate MMP2 expression via its competing endogenous RNA activity on miR-3182 at the posttranscriptional level. Taken together, our study has elucidated the role of oncogenic ODRUL in OS progression and may provide a new target in OS therapy.

Zhu KP ，Ma XL ，Zhang CL 《-》

LncRNA ODRUL regulates progression of osteosarcoma by regulating IL-6 via sponging miR-6874-3p.

Accumulating evidence has shown that many long non-coding RNAs (lncRNA) participate in the tumorigenesis, including osteosarcoma (OS). Of them, lncRNA ODRUL was previously reported to act as a possible oncogene in OS doxorubicin resistance. However, the underlying molecular mechanism of ODRUL involved in the progression of OS still remains to be thoroughly investigated. In the current study, we reported another mechanism by which ODRUL regulates OS progression. QRT-PCR and WB were conducted to detect ODRUL, miR-6874-3p and IL-6 expression in OS tissues and cells. The Kaplan-Meier was used to assess the relevance between the expression level of miR-6874-3p and the overall survival of OS patients. Wound healing assays and Transwell assays were used to evaluate the invasion and migration of OS cells. Furthermore, the binding sites of ODRUL and IL-6 to miR-6874-3p were predicted by bioinformatics and verified by dual-luciferase reporter gene assays. ODRUL and IL-6 were highly expressed in OS cells and tissues, while miR-6874-3p was expressed at low levels. The overall survival of high miR-6874-3p expression of OS patients was longer than that of low miR-6874-3p expression of OS patients. MiR-6874-3p overexpression markedly inhibited the progression of OS cells. Both ODRUL and IL-6 could bind to miR-6874-3p at the predicted binding sites which were authenticated by dual-luciferase reporter gene assay. MiR-6874-3p could inhibit OS cell proliferation and metastasis and ODRUL could reverse the suppression induced by miR-6874-3p in vivo. In conclusion, ODRUL could effectively sponge miR-6874-3p to upregulate the expression of IL-6 in OS progression.

Zhan T ，Zhu K ，Hu J ，Ma X ，Zhu Y ，Zhang C ... -  《-》

A long non-coding RNA contributes to doxorubicin resistance of osteosarcoma.

Zhang CL ，Zhu KP ，Shen GQ ，Zhu ZS ... -  《-》

Antisense lncRNA FOXF1-AS1 Promotes Migration and Invasion of Osteosarcoma Cells Through the FOXF1/MMP-2/-9 Pathway.

Kun-Peng Z ，Chun-Lin Z ，Xiao-Long M 《International Journal of Biological Sciences》

LINC01128 regulates the development of osteosarcoma by sponging miR-299-3p to mediate MMP2 expression and activating Wnt/β-catenin signalling pathway.

Osteosarcoma (OS) is one of the most common metastatic bone cancers, which results in significant morbidity and mortality. The important role of long non-coding RNAs (lncRNAs) in the biological processes of OS has been demonstrated through several studies. In the current study, we evaluated the role of the lncRNA, LINC01128, in OS. We analysed the expression of LINC01128 in three OS gene expression omnibus (GEO) data sets GSE21257, GSE36001 and GSE42352. The expression of LINC01128 in OS tissues and matched non-tumour tissues obtained from 50 OS patients was detected using qRT-PCR. The association between LINC01128 expression and overall survival of OS patients was evaluated using the Kaplan-Meier method. The effects of LINC01128 knockdown and overexpression were evaluated through in vitro and in vivo assays. The LINC01128/miR-299-3p/ MMP2 axis was verified using dual-luciferase reporter assay and qRT-PCR assays. GEO data sets analysis revealed that the expression of LINC01128 was increased in OS. Elevated LINC01128 expression was accompanied by shorter overall survival in OS patients. Functional studies revealed that LINC01128 knockdown reduced the proliferation, migration and invasion of OS cells both in vitro and in vivo. Mechanistically, LINC01128 sponged miR-299-3p to increase MMP2 expression. Rescue assays determined the role of the LINC01128/miR-299-3p/MMP2 axis in the proliferation, migration and invasion of OS cells. Additionally, the Wnt/β-catenin signalling pathway was activated by LINC01128 and MMP2 in OS cell lines. In summary, this study demonstrates that LINC01128 facilitates OS by functioning as a sponge of miR-299-3p, thus promoting MMP2 expression and activating the Wnt/β-catenin signalling pathway.

Yao Q ，Chen T 《-》