MicroRNA-302a targets GAB2 to suppress cell proliferation, migration and invasion of glioma

Abstract

Glioma is the most frequent and aggressive primary tumor of the brain in humans. Over the last few decades, significant progress has been made in early detection and multi-mode treatments, but the prognosis of gliomas is still extremely poor. MicroRNAs are endogenously expressed non-coding, single strand and short RNA molecules. Increasing number of studies demonstrated that microRNAs are dysregulated in a variety of human cancers, and play significant roles in tumorigenesis and tumor development, including glioma. In the present study, we for the first time found that microRNA-302a (miR-302a) was significantly downregulated in both glioma tissues and cell lines. In glioma patients, low miR-302a expression was correlated with KPS score and WHO grade. Restoration of miR-302a expression inhibited cell proliferation, migration and invasion of glioma in vitro. In addition, GAB2 was identified as a direct target of miR-320a. In clinical glioma tissues, GAB2 was upregulated and in-versely correlated with miR-302a expression. GAB2 underexpression had similar biological roles with miR-302a overexpression in glio-ma cells, further confirming that GAB2 was a functional downstream target of miR-302a. Moreover, rescue experiments showed that upregulation of GAB2 effectively reversed the inhibition effects of miR-302a on glioma cells proliferation, migration and invasion. These findings suggested that miR-302a is an important tumor suppressor of glioma progression by directly targeting GAB2, thus providing new insight into the molecular mechanisms underlying glioma occurrence, development and evolution of glioma.

P53-regulated miR-320a targets PDL1 and is downregulated in malignant mesothelioma

“…We then focused specifically on miRNA-320a, which was recently shown to act as a tumor suppressor in different cancer types in which it was found downregulated, such as colorectal 30 , 31 , breast 32 , 33 , bladder 34 , lung 35 – 37 , prostate 38 and gastric cancer 39 , 40 , multiple myeloma 41 and gliomas 42 – 44 .…”

miR‑128‑3p inhibits glioma cell proliferation and differentiation by targeting NPTX1 through IRS‑1/PI3K/AKT signaling pathway

“…It has been proved that overexpression of miR-497 is associated with resistance to temozolomide in human glioma cells by targeting mammalian target of rapamycin/B-cell lymphoma 2 (26). It has also been reported that miR-302a is an important tumor suppressor of glioma progression by directly targeting GRB2-associated binding protein, thus providing novel insight into the molecular mechanisms underlying the genesis, development and progression of glioma (27). Furthermore, miR-128-3p was reported to be closely associated with lung cancer (13), hepatocellular carcinoma (14,15) and gastric cancer (28).…”

MicroRNA-379 acts as a tumor suppressor in non-small cell lung cancer by targeting the IGF-1R-mediated AKT and ERK pathways

“…gastric cancer (18), hepatocellular carcinoma (19), prostate cancer (20), renal cell carcinoma (21), glioma (22) and lung cancer (23). Moreover, numerous studies reported that the dysregulation of miRNAs is involved in tumorigenesis and tumor development; some miRNAs act as an oncogene or tumor suppressor gene in human cancers, depending on the regulated tumor forms and their specific target genes (24).…”