Overexpression of miR-29a reduces the oncogenic properties of glioblastoma stem cells by downregulating Quaking gene isoform 6

Abstract

Glioblastoma is the most common type of malignant primary brain tumor and has high recurrence and lethality rates. Glioblastoma stem cells (GSCs), a subpopulation of glioblastoma cells, may promote rapid tumor recurrence and therapy resistance. Because altered microRNA (miR) expression in GSCs may lead to glioblastoma progression, we assessed the effects of miR-29a expression on the oncogenic behavior of GSCs. MiR-29a expression was lower in GSCs than non-GSCs, and overexpression of miR-29a in GSCs inhibited cell proliferation, migration and invasion, but promoted apoptosis. MiR-29a directly inhibited the expression of Quaking gene isoform 6 (QKI-6) by binding to its 3′-UTR, and thus inhibited GSC malignant behavior. In addition, Wilms’ tumor 1-associating protein (WTAP) was identified as a downstream target of QKI-6. Overexpression of miR-29a in GSCs inhibited expression of WTAP and suppressed both phosphoinositide 3-kinase/AKT and extracellular signal-related kinase pathways by downregulating QKI-6, thereby inhibiting cell proliferation, migration, and invasion but promoting apoptosis. We have characterized a novel miR-29a/QKI-6/WTAP axis in GSCs, which may provide theoretical support for the treatment of glioblastoma with miR-29a agomirs.

Assessment of the Diagnostic Potential of miR-29a-3p and miR-92a-3p as Circulatory Biomarkers in Acute Myeloid Leukemia

“…Similar Results were reported by other study groups (Zhu et al, 2013;Gong et al, 2014;Xu et al, 2014) who reported a downregulation in miR-29a/29b levels in peripheral blood mononuclear cells and bone marrow from AML patients compared with healthy individuals. Also, miR-29a was found to be downregulated in many other types of neoplasms like lung cancer (Barkley and Santocanale, 2013), oral squamous carcinoma (Lu et al, 2014), glioblastoma (Xi et al, 2017), metastatic prostate cancer (Ahmed et al, 2013), ALK-positive anaplastic large cell lymphomas (Desjobert et al, 2011), endocrine-sensitive breast cancer (Muluhngwi et al, 2017).…”

The Emerging Roles of RNA Modifications in Glioblastoma

“…WTAP stimulates tumorigecity, migration and invasion of GBM cells possibly through enhancing the activity of epidermal growth factor receptor (EGFR), an important oncogenic factors in GBM [61]. In GSCs, WTAP also plays an important role as a downstream target of miR-29a/Quaking gene isoform 6 (QKI-6) axis-mediated inhibition of cell proliferation, migration and invasion, as well as promotion of apoptosis in GSCs [63].…”

The interplay between m6A RNA methylation and noncoding RNA in cancer

“…In addition to controlling their own cleavage, localization, transport, stability, and degradation [13,14,[35][36][37], noncoding RNAs regulate the biological functions of cells, including the proliferation, infiltration, and metastasis of certain tumor cells [1,[17][18][19][20][21][22]. Surprisingly, it was revealed that noncoding RNAs also have a regulatory effect on m6A modifications [38][39][40][41]. Thus, concomitant targeting of m6A and noncoding RNAs may provide a synergistic effect in cancer therapy.…”