LINC00202 promotes retinoblastoma progression by regulating cell proliferation, apoptosis, and aerobic glycolysis through miR-204-5p/HMGCR axis

Abstract

<jats:title>Abstract</jats:title><jats:p>LINC00202 is a newly identified long noncoding RNA (lncRNA) and has been demonstrated to involve in the progression of retinoblastoma (RB). Here, we further explored the role and the underlying molecular mechanism of LINC00202 on RB malignant properties and glycolysis. LINC00202, microRNA (miR)-204-5p, and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) mRNA were detected by a quantitative real-time polymerase chain reaction. Cell proliferation and apoptosis were analyzed using cell counting kit-8 assay and colony formation assay and flow cytometry, respectively. Glucose metabolism was calculated by measuring the extracellular acidification rate (ECRA). Western blot was used to detect the levels of HMGCR, ki67, pro-caspase-3, cleaved-caspase-3, and lactate dehydrogenase A chain (LDHA). The interaction between miR-204-5p and LINC00202 or HMGCR was analyzed by the dual-luciferase reporter assay. Murine xenograft model was established to conduct <jats:italic>in vivo</jats:italic> experiments. LINC00202 expression was upregulated in RB tumor tissues and LINC00202 knockdown inhibited RB cell proliferation, glycolysis, and stimulated apoptosis <jats:italic>in vitro</jats:italic> as well as impeded tumor growth <jats:italic>in vivo</jats:italic>. MiR-204-5p directly bound to LINC00202 and HMGCR in RB cells, and LINC00202 functioned as a competing endogenous RNA in regulating HMGCR through competitively binding to miR-204-5p. More importantly, the regulation of malignant properties and glycolysis of RB cells mediated by LINC00202 could be reversed by abnormal miR-204-5p or HMGCR expression in RB cells. In all, LINC00202 promoted RB cell proliferation, glycolysis, and suppressed apoptosis by regulating the miR-204-5p/HMGCR axis, suggesting a novel therapeutic target for patients with RB.</jats:p>

The clinical diagnostic value of plasma miR-592 and miR-217-3p levels in retinoblastoma

“…For example, the expression of miR-204 in Rb patients is dysregulated, and its expression level is related to optic nerve infiltration, lymph node metastasis, and tumour tissue differentiation. miR-204 may affect the proliferation and apoptosis of Rb cells, thereby affecting the development of Rb, which may become an early stage molecular indicator for diagnosing and evaluating the prognosis of Rb (43)(44)(45); miR-338-5p is up-regulated in the serum of patients with Rb, which may play a role in promoting cancer in the occurrence and development of Rb, and has the potential value of the early diagnosis of Rb (46,47). Recent studies have shown that dysregulated miR-592 and miR-217-3p have been reported to be involved in developing many different types of cancer.…”