Abstract
Glioma is a type of malignant intracranial tumor. Extensive research has identified the participation of long noncoding RNAs (lncRNAs) in glioma progression. This study investigated the mechanism of LINC00294 in mitochondrial function and glioma cell apoptosis. Glioma miRNA and mRNA microarray datasets were obtained, and differentially expressed lncRNAs in glioma were screened through various databases. The LINC00294 expression in glioma patients and glioma cells was detected. Glioma cells were treated under hypoxic conditions and transfected with LINC00294 silencing. The apoptosis and mitochondrial function of glioma cells were measured. The expressions of and relations among miR-21-5p, CASKIN1, and cAMP in glioma cells were analyzed. Under hypoxic conditions and LINC00294 silencing, the apoptosis and mitochondrial function of glioma cells were detected after inhibiting miR-21-5p or overexpressing CASKIN1. Our results indicated that LINC00294 was downregulated in glioma. LINC00294 silencing inhibited glioma cell apoptosis under hypoxia. LINC00294 silencing reversed the inhibition of hypoxia on mitochondrial function under hypoxia. LINC00294 promoted the CASKIN1 expression by sponging miR-21-5p and activated the cAMP pathway. Inhibition of miR-21-5p or overexpression of CASKIN1 annulled the effects of LINC00294 silencing on mitochondrial function and glioma cell apoptosis under hypoxia. In conclusion, LINC00294 elevated the CASKIN1 expression by sponging miR-21-5p and activating the cAMP signaling pathway, thus inhibiting mitochondrial function and facilitating glioma cell apoptosis.
Highlights
Glioma is regarded the most common primary intracranial malignancy, which may occur in any part of the central nervous system; it elicits predominant manifestation in the brain and glial tissues [1]
The long noncoding RNAs (lncRNAs) predicted for regulation by competing endogenous RNA (ceRNA) in TCGA were identified through the lncACTdb database, from which 7 candidate lncRNAs (Supplementary Table 1) were obtained from intersection of predicted results and microarray analysis results (Figure 1(c))
LINC00294 was differentially expressed in the 57 cases of glioma (Figure 1(d)), with a low expression pattern of LINC00294 serving as an indicator of poor prognosis (Figure 1(e))
Summary
Glioma is regarded the most common primary intracranial malignancy, which may occur in any part of the central nervous system; it elicits predominant manifestation in the brain and glial tissues [1]. Previous exposure to ionizing radiation has been identified as a definitive risk factor for malignant glioma, and multiple ongoing studies are assessing the genetic risk factors for glioma [2]. The management of glioma presents with enormous clinical challenges, due to their characteristic tumor location and because of their malignant biological characteristics, with a high tendency of proliferation, invasion, angiogenesis, and metabolic abnormality [3]. The currently available medical treatments, including maximal safe resection, external beam radiation, and chemotherapy, can extend the median overall survival of glioma patients up to 12-18 months [4]. Several recent studies have sought to determine the underlying molecular mechanism and biomarkers of glioma for the development of molecular targeted therapies for glioma patients. Only limited molecular mechanisms have been determined with clinical application. The identification of potent diagnostic and prognostic biomarkers is warranted for effective intervention of glioma
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