MiR-511 mimic transfection inhibits the proliferation, invasion of osteosarcoma cells and reduces metastatic osteosarcoma tumor burden in nude mice via targeting MAPK1

Abstract

Osteosarcoma, a highly aggressive cancer, can rapidly metastasize to distant organs such as lung, liver, brain. Despite much progress in the therapeutic regime has been made, the prognosis of osteosarcoma remains poor. In present study, microRNA-511 (miR-511) is lowly expressed in osteosarcoma cells, including MG63, U-2 OS, Saos-2 cells, while mitogen activated protein kinase1 (MAPK1) is highly expressed in osteosarcoma cells. Interestingly, MAPK1 might be a target of miR-511. We found that overexpression of miR-511 by miR-511 mimic transfection may result to low expression of MAPK1. Further study showed that miR-511 mimic inhibits the development of osteosarcoma MG63 cell, including proliferation and invasion. Moreover, miR-511 mimic transfection reduces metastatic osteosarcoma tumor burden in nude mice. These activities are mediated by targeting MAPK1. Our study provides a new sight for the molecular pathogenesis of osteosarcoma.

Tumor-Released Products Promote Bone Marrow-Derived Macrophage Survival and Proliferation

“…Zhang et al [46] reported that overexpression of miR-511 promoted hepatocellular carcinoma proliferation by targeting B cell translocation gene 1 (BTG1). However, in a model of osteosarcoma it was demonstrated that miR-511 transfection resulted in lower expression of mitogen-activated protein kinase 1 (MAPK1) which inhibited osteosarcoma MG63 cell proliferation and invasion [47]. Nevertheless, there is no evidence for a role of miR-511 in macrophage proliferation.…”

Identification of a novel autophagy-related gene signature for predicting metastasis and survival in patients with osteosarcoma

“…Univariate Cox regression and Lasso Cox regression analysis showed that a gene signature composed of 9 autophagy-related genes (BNIP3, MYC, BAG1, CALCOCO2, ATF4, AMBRA1, EGFR, MAPK1, and PEX3) was closely related to the prognosis of OS. Studies have shown that the abnormal expression of MYC [52], ATF4 [53], and MAPK1 [54] is related to the proliferation, migration, and invasion of OS cells. As a transcription target of MYC, BAG1 cooperates with HSP70 molecular chaperone to selectively mediate MYC overexpression and affect the survival of OS cells [55].…”

Identification of potential crucial genes and key pathways in osteosarcoma

“…For instance, by conducting bioinformatics analysis on three datasets deposited in GEO database (GSE36001, GSE19276 and GSE16088), Pan Liu et al [ 10 ] revealed that tumor protein p53 (TP53), mitogen-activated protein kinase 1 (MAPK1), estrogen receptor 1 (ESR1), notch homolog protein 3 (NOTCH3) and caspase 1 (CASP1) might potentially be important osteosarcoma-associated genes. Among them, mutant TP53 was subsequently reported to be associated with poor survival of osteosarcoma patients, because it can increase the cell proliferation, migration, and chemoresistance in osteosarcoma [ 12 ]; MAPK1 has been confirmed to be highly expressed in osteosarcoma cells, and can be down-regulated by osteosarcoma related tumor suppressive miR-511 [ 13 ]. Based on this, regulation of MAPK1 receptor expression may be a novel approach to treat osteosarcoma.…”