MiR-100 Inhibits Osteosarcoma Cell Proliferation, Migration, and Invasion and Enhances Chemosensitivity by Targeting IGFIR

Abstract

MicroRNAs are highly conserved noncoding RNA that negatively modulate protein expression at a posttranscriptional and/or translational level. MicroRNAs play an important role in the development and progression of human cancers, including osteosarcoma. Recent studies have shown that miR-100 was downregulated in many cancers; however, the role of miR-100 in human osteosarcoma has not been totally elucidated. In this study, we demonstrate that the expression of miR-100 was significantly downregulated in human osteosarcoma tissues compared to the adjacent tissues. Enforced expression of miR-100 inhibited cell proliferation, migration, and invasion abilities of osteosarcoma cells, U-2OS, and MG-63. Additionally, miR-100 also sensitized osteosarcoma cells to cisplatin and promoted apoptosis. Furthermore, overexpression of miR-100 decreased the expression of insulin-like growth factor I receptor and inhibited PI3K/AKT and MAPK/ERK signaling. In human clinical specimens, insulin-like growth factor I receptor was inversely correlated with miR-100 in osteosarcoma tissues. Collectively, our results demonstrate that miR-100 is a tumor suppressor microRNA and indicate its potential application for the treatment of osteosarcoma in future.

Cisplatin-resistant lung cancer cell–derived exosomes increase cisplatin resistance of recipient cells in exosomal miR-100–5p-dependent manner

“…27,28 Several researches proved that overexpression of miR-100 can sensitize cancer cells to DDP in various tumors. 23,29 Concurring with these studies, our research confirmed that the downregulated expression of miR-100-5p contributed to DDP resistance in lung cancer cells. The luciferase reporter in previous literatures 22,23 proved that mTOR is a direct target gene of miR-100-5p and can be regulated by directly binding to the 3′-UTR of mTOR.…”

Biglycan Regulates MG63 Osteosarcoma Cell Growth Through a LPR6/β-Catenin/IGFR-IR Signaling Axis

“…Since in the present study, we showed an enhancement of biglycan expression through IGF-IR downstream effects we examined the possible involvement of IGF-IR in biglycan-dependent osteosarcoma cell growth. Indeed, in this study IGF-IR downstream signaling, was shown to be a strong endogenous enhancer of MG63 cell growth, in keeping with previous reports ( 47 , 49 ). Importantly, IGF-I/IGF-IR dependent growth was completely abrogated in biglycan-deficient cells.…”

“…We further investigated if other potential mediators of biglycan action involved in key developmental processes such as BMP, Wnt/β-catenin, RUNX2, HIPPO/YAP or IGF-IR are “hijacked” by osteosarcoma ( 45 ) Previously, IGF-I was shown to be an important enhancer of osteosarcoma cell survival facilitating growth and attenuating apoptosis ( 46 ). Furthermore, IGF-IR is upregulated in osteosarcoma tissue samples as recently shown by Liu et al ( 47 ) whereas the genetic polymorphisms of IGF-I were shown to be correlated with osteosarcoma risk and prognosis ( 48 ). Since in the present study, we showed an enhancement of biglycan expression through IGF-IR downstream effects we examined the possible involvement of IGF-IR in biglycan-dependent osteosarcoma cell growth.…”

MicroRNA‑100 functions as a tumor suppressor in cervical cancer via downregulating the SATB1 expression and regulating AKT/mTOR signaling pathway and epithelial‑to‑mesenchymal transition

“…Previous studies demonstrated that miR-100 exerted tumor suppressive functions in numerous cancers by modulating different targets. For instance, Liu et al ( 26 ) proposed that miR-100 repressed cell proliferation, invasion and migration and promoted chemosensitivity in osteosarcoma via regulating IGFIR; Luan et al ( 27 ) proposed that miR-100 upregulation suppressed glioblastoma cell chemosensitivity, proliferation and migration through FGFR3; studies by Qureshi et al ( 28 ) demonstrated that miR-100 was a novel non-invasive biomarker for earlier diagnosis of bladder cancer. Thus, we assumed that miR-100 might serve as a cancer repressor in CC.…”