AC016405.3, a novel long noncoding RNA, acts as a tumor suppressor through modulation of TET2 by microRNA‐19a‐5p sponging in glioblastoma. Issue 5 (23rd April 2019)

• Record Type: Journal Article
• Authors: Ren, Siyang; Xu, Yinghui
• Is Part Of: Cancer science. Volume 110:Issue 5(2019)
• Page Start: 1621
• Page End: 1632
• Publication Date: 2019-04-23
• Subjects: ceRNA -- glioblastoma -- lncRNA AC016405.3 -- miR‐19a‐5p -- proliferation/metastasis; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14002
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : Long non‐coding RNAs (lncRNAs) are crucial regulators in various malignancies including glioblastoma multiforme (GBM). In the present study, we screened out a new lncRNA, AC016405.3, through a previous genome‐wide lncRNA microarray analysis in GBM. It showed that AC016405.3 was downregulated in GBM tissue specimens and cell lines, and it also illustrated that the downregulated AC016405.3 was closely correlated with several aggressive features of patients with GBM. Functionally, we found that overexpression of AC016405.3 suppressed GBM cells' proliferation and metastasis using a gain of function experiment. We further showed that microRNA (miR)‐19a‐5p, a carcinogenic miRNA, was a downstream miRNA of AC016405.3. AC016405.3 was revealed as a target of miR‐19a‐5p, and overexpression of miR‐19a‐5p reversed the inhibitive effect of AC016405.3 on GBM cell proliferation and metastasis. Furthermore, a novel downstream gene of miR‐19a‐5p, TET2, was identified through a constructed microarray analysis. We showed that TET2 was downregulated in GBM and was involved in miR‐19a‐5p‐mediated proliferation and metastasis by directly being targeted. Finally, through a western blot assay and a series of functional CCK‐8 and metastatic assays, we showed that AC016405.3 suppressed proliferation and metastasis through modulation of TET2 by sponging of miR‐19a‐5p in GBM cells. In summary, the findings of the current study identified a novel lncRNA and illustrated that AC016405.3, acting as an anti‐oncogene, suppressed GBM cell proliferation and metastasis by regulating TET through miR‐19a‐5p sponging. Our present study might provide a new axis in the molecular treatment of GBM. Abstract : We found a novel anticarcinogenetic long noncoding RNA, AC016405.3, that was downregulated in glioblastoma. Functionally, we showed that AC016405.3 suppressed proliferation and metastasis of glioblastoma cells. Mechanically, we determined that AC016405.3 suppressed TET2‐mediated proliferation and metastasis by acting as a competing endogenous RNA of microRNA‐19a‐5p.