miR-23a promotes invasion of glioblastoma via HOXD10-regulated glial-mesenchymal transition

Abstract

Glioblastoma is the most aggressive and invasive brain tumor and has a poor prognosis; elucidating the underlying molecular mechanisms is essential to select molecular targeted therapies. Here, we investigated the effect of microRNAs on the marked invasiveness of glioblastoma. U373 glioblastoma cells were infected with 140 different microRNAs from an OncomiR library, and the effects of the invasion-related microRNAs and targeted molecules were investigated after repeated Matrigel invasion assays. Screening of the OncomiR library identified miR-23a as a key regulator of glioblastoma invasion. In six glioblastoma cell lines, a positive correlation was detected between the expression levels of miR-23a and invasiveness. A luciferase reporter assay demonstrated that homeobox D10 (HOXD10) was a miR-23a-target molecule, which was verified by high scores from both the PicTar and miRanda algorithms. Forced expression of miR-23a induced expression of invasion-related molecules, including uPAR, RhoA, and RhoC, and altered expression of glial-mesenchymal transition markers such as Snail, Slug, MMP2, MMP9, MMP14, and E-cadherin; however, these changes in expression levels were reversed by HOXD10 overexpression. Thus, miR-23a significantly promoted invasion of glioblastoma cells with polarized formation of focal adhesions, while exogenous HOXD10 overexpression reversed these phenomena. Here, we identify miR-23a-regulated HOXD10 as a pivotal regulator of invasion in glioblastoma, providing a novel mechanism for the aggressive invasiveness of this tumor and providing insight into potential therapeutic targets.

Exosomes with low miR-34c-3p expression promote invasion and migration of non-small cell lung cancer by upregulating integrin α2β1

“…All assays were performed in quadruplicate and were repeated three times. 40 Immunoprecipitation Treated cells were collected and lysed in IP buffer (150 mM NaCl, 50 mM Tris HCl, 1% v/v Triton X-100 and 1 mM EDTA) containing phosphatase and protease inhibitors. Subsequently, the cell lysates (1 mg/mL) were incubated with antibodies against integrin α2 and integrin β1 overnight at 4°C.…”

miR‐5188 augments glioma growth, migration and invasion through an SP1‐modulated FOXO1‐PI3K/AKT‐c‐JUN‐positive feedback circuit

“…Accumulating reports have supported that microRNAs (miR-NAs) participated in numerous processes, including development, proliferation, cell cycle control and cellular differentiation, and are involved in regulating many human cancers. [5][6][7][8][9][10][11] miRNAs may serve as tumour suppressors or oncogenes depending on the cancer type.…”

RETRACTED ARTICLE: Silencing hsa_circ_PVT1 (circPVT1) suppresses the growth and metastasis of glioblastoma multiforme cells by up-regulation of miR-199a-5p

“…MiRNAs as a category of small noncoding RNA acts a critical factor of gene expression by promoting mRNA degradation or preventing the translation of target mRNA [14,15]. MiRNA has been investigated in a variety of human diseases, and plays a vital part in cell proliferation, metastasis and EMT process [15].…”