Abstract
Long noncoding RNA (lncRNA) LINC00461 (LINC00461) is reported to be related to glioma progression. However, the mechanism of LINC00461 in glioma remains unclear. Expression of LINC00461, miRNA (miR)-216a, and aquaporin 4 (AQP4) was detected using real-time quantitative PCR (RT-qPCR) and western blotting. Proliferation, temozolomide (TMZ) resistance, migration, and invasion were assessed by MTT, colony formation, and transwell assays, respectively. The target binding among miR-216a, LINC00461, and AQP4 was confirmed by the luciferase reporter assay. The tumor growth was monitored in the xenograft experiment. LINC00461 was upregulated, and miR-216a was downregulated in glioma tissues and cells, and LINC00461 upregulation was correlated with large tumor size, higher WHO grade and recurrence, and poor overall survival. LINC00461 knockdown suppressed cell viability, abilities of cell cloning and migration and invasion, and TMZ resistance in glioma. Mechanically, LINC00461 was confirmed to sponge miR-216a to affect AQP4 expression. Rescue assays verified that miR-216a downregulation or AQP4 upregulation abrogated the inhibitory effect of LINC00461 knockdown on cell proliferation, migration, invasion, and TMZ resistance in vitro. Moreover, LINC00461 downregulation blocked the glioma tumor growth in vivo. In conclusion, LINC00461 knockdown inhibits glioma cell proliferation, migration, invasion, and TMZ resistance through miR-216a/AQP4 axis, suggesting LINC00461 as an oncogene in glioma progression.
Highlights
Human glioma is one of the most prevalent and aggressive malignant tumors in the human central nervous system with high mortality worldwide [1]
Human LINC00461 wild-type (LINC00461 WT) and aquaporin 4 (AQP4) 3′ UTR fragment wild-type (AQP4 WT) containing the potential binding sites of hsa-miR-216a were cloned by PCR methods into psi-CHECK vector (Invitrogen), as well as the mutant types
U251 and A172 cells were cotransfected with miR-216a/NC mimics and either LINC00461 WT/MUT or AQP4 WT/MUT
Summary
Human glioma is one of the most prevalent and aggressive malignant tumors in the human central nervous system with high mortality worldwide [1]. It is known that glioma arises from astrocytes or astroglial precursors [2]. The World Health Organization (WHO) has divided glioma into four grades: I–IV [3]. The prognosis of glioma remains poor, and the 5-year survival rate of glioma patients in low grade (grades I–II) is 30–70%, while the median survival time of glioblastoma multiform (grade IV) is less than 12 months [4]. The rates of recurrence and mortality are still high because of unrestricted proliferation and extensive metastasis of glioma tumors [5]. It is imperative to focus on the special molecular mechanisms of glioma tumorigenesis and progression
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