Abstract 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 in vivo experiments. LINC00202 expression was upregulated in RB tumor tissues and LINC00202 knockdown inhibited RB cell proliferation, glycolysis, and stimulated apoptosis in vitro as well as impeded tumor growth in vivo. 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.

中文翻译：

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LINC00202通过miR-204-5p/HMGCR轴调节细胞增殖、凋亡和有氧糖酵解促进视网膜母细胞瘤进展

摘要 LINC00202 是一种新发现的长链非编码 RNA (lncRNA)，已被证明参与视网膜母细胞瘤 (RB) 的进展。在这里，我们进一步探讨了 LINC00202 对 RB 恶性特性和糖酵解的作用和潜在分子机制。LINC00202、microRNA (miR)-204-5p 和 3-羟基-3-甲基-戊二酰辅酶 A 还原酶 (HMGCR) mRNA 通过定量实时聚合酶链反应检测。分别使用细胞计数试剂盒-8 测定和集落形成测定和流式细胞术分析细胞增殖和凋亡。通过测量细胞外酸化率（ECRA）计算葡萄糖代谢。Western印迹用于检测HMGCR、ki67、pro-caspase-3、cleaved-caspase-3和乳酸脱氢酶A链（LDHA）的水平。miR-204-5p 和 LINC00202 或 HMGCR 之间的相互作用通过双荧光素酶报告基因测定进行分析。建立小鼠异种移植模型以进行体内实验。LINC00202 表达在 RB 肿瘤组织中上调，LINC00202 敲低可抑制 RB 细胞增殖、糖酵解，并在体外刺激细胞凋亡，并在体内阻碍肿瘤生长。MiR-204-5p 直接与 RB 细胞中的 LINC00202 和 HMGCR 结合，而 LINC00202 通过与 miR-204-5p 竞争性结合，作为竞争性内源性 RNA 调节 HMGCR。更重要的是，LINC00202介导的RB细胞恶性特性和糖酵解的调节可以通过RB细胞中异常的miR-204-5p或HMGCR表达来逆转。总之，LINC00202 促进了 RB 细胞增殖、糖酵解、