MicroRNAs involved in chemo- and radioresistance of high-grade gliomas

Abstract

High-grade gliomas (HGGs) are malignant primary brain tumors of glial cell origin. Despite optimal course of treatment, including maximal surgical resection followed by adjuvant chemo- and/or radiotherapy, the prognosis still remains poor. The main reason is the commonly occurring chemo- and radioresistance of these tumors. In recent years, several signaling pathways, especially PI3K/AKT and ATM/CHK2/p53, have been linked to the resistance of gliomas. Moreover, additional studies have shown that these pathways are significantly regulated by microRNAs (miRNAs), short endogenous RNA molecules that modulate gene expression and control many biological processes including apoptosis, proliferation, cell cycle, invasivity, and angiogenesis. MiRNAs are not only highly deregulated in gliomas, their expression signatures have also been shown to predict prognosis and therapy response. Therefore, they present promising biomarkers and therapeutic targets that might overcome the resistance to treatment and improve prognosis of glioma patients. In this review, we summarize the current knowledge of the functional role of miRNAs in gliomas resistance to chemo- and radiotherapy.

IKKα-mediated biogenesis of miR-196a through interaction with Drosha regulates the sensitivity of cancer cells to radiotherapy

“…Several signaling pathways, including PI3K/AKT, mitogen-activated protein kinase and ATM/CHK2/p53, have been linked to the tumor radioresistance. 22,23 In the present study we have demonstrated that IKKα-mediated miR-196a biogenesis regulates the sensitivity of NPC cells to radiotherapy. Dephosphorylation of p-IKKαT23 downregulates miR-196a expression and promotes the resistance of NPC cells to radiation treatment.…”

Investigating molecular alterations to profile short- and long-term recurrence-free survival in patients with primary glioblastoma

“…The interplay between the various matrix and growth factor receptors, and the activation of signaling pathways that facilitate the invasion of tumor cells, has been recently recognized as a composite, dynamic consequence of altered cell-cell adhesion, proteolytic remodeling and synthesis of ECM, and selective expression and activation of integrins (10). Furthermore, in the past few years, several signaling pathways have been associated with reduced sensitivity of GB cells to radiation and chemotherapy (11). Numerous genes involved in these pathways have been demonstrated to be regulated by microRNAs (miRNAs), which are important regulators in cancer cell biology, and promising biomarkers or therapeutic targets in GB (11,12).…”

“…Furthermore, in the past few years, several signaling pathways have been associated with reduced sensitivity of GB cells to radiation and chemotherapy (11). Numerous genes involved in these pathways have been demonstrated to be regulated by microRNAs (miRNAs), which are important regulators in cancer cell biology, and promising biomarkers or therapeutic targets in GB (11,12). However, despite all the molecular information on GB gathered thus far, the optimal management of patients with GB remains elusive, due to the absence of validated data from clinical studies, and the great heterogeneity of this fragile subpopulation, in terms of their physical condition, co-morbidity status, tolerance to treatment and clinical prognosis (13).…”

Knockdown of microRNA-1323 restores sensitivity to radiation by suppression of PRKDC activity in radiation-resistant lung cancer cells

“…Previous studies have used miRNA arrays to identify different miRNA expression profiles that are associated with cancer initiation and progression (23)(24)(25). In the present study, high-throughput sequencing technology was applied to discover novel miRNAs associated with radioresistance.…”