miR-141-3p functions as a tumor suppressor modulating activating transcription factor 5 in glioma

Glioma is the most common malignant primary brain tumor which arises from the central nervous system. Our studies reported that an anti-apoptotic factor, activating transcription factor 5 (ATF5), is highly expressed in malignant glioma specimens and cell lines. Downregulation by dominant-negetive ATF5 could repress glioma cell proliferation and accelerate apoptosis. Here, we further investigate the upstream factor which regulates ATF5 expression. Bioinformatic analysis showed that ATF5 was a potential target of miR-141-3p. Luciferase reporter assay verified that miR-141-3p specifically targeted the ATF5 3′-UTR in glioma cells. Functional studied suggested that miR-141-3p overexpression inhibited proliferation and promoted apoptosis of glioma cells (U87MG and U251). Xenograft experiments proved the inhibition of miR-141-3p on glioma growth in vivo. Moreover, exogenous ATF5 without 3′-UTR restored the cell proliferation inhibition triggered by miR-141-3p. Taken together, we put forward that miR-141-3p is a new upstream target towards ATF5. It can serve as a crucial tumor suppressor in regulating the ATF5-regulated growth of malignant glioma. - Highlights: • ATF5 was highly expressed in gliomas and was essential for cell proliferation and apoptosis. • MiR-141-3p specifically targeted the ATF5 3′-UTR in glioma cells. • MiR-141-3p was significantly downregulated in glioma tissues and cell lines. • MiR-141-3p inhibited glioma growth through repressing ATF5 expression in vitro and in vivo. • Exogenous expression of ATF5 rescued cells from proliferation inhibition triggered by miR-141-3p.