Glioblastoma (GBM) remains the most common and malignant tumor of the human central nervous system. Increasing evidence has highlighted that tumor cells with high transferrin receptor (TFRC) expression show advantages in growth. Long noncoding RNAs (lncRNAs) are related to glioma progression by mediating microRNAs (miRNAs). However, the underlying mechanism among TFRC, miRNA and lncRNA in GBM is limited. In the current study, we identified a new lncRNA-induced signaling mechanism that regulates the TFRC levels in GBM. The TFRC level was higher in glioma cell lines, and elevated TFRC expression promoted the proliferation and survival of glioma cells. Further study showed that hsa-miR-144a-3p bound to the 3′-UTR of TFRC mRNA and inhibited its expression, preventing the malignant properties of glioma cells, such as proliferation and survival. We also found that the lncRNA RP1-86C11.7 sponges hsa-miR-144-3p to suppress its protective role in glioma. RP1-86C11.7 overexpression in glioma cells elevated TFRC expression, increased the intracellular free iron level, and deteriorated oncogenicity, with a significant reduction in hsa-miR-144-3p. By contrast, silencing RP1-86C11.7 upregulated the hsa-miR-144-3p level, resulting in decreased TFRC expression and repressed glioma progression. However, the effect of silencing RP1-86C11.7 was reversed with simultaneous hsa-miR-144-3p inhibitor treatment: the TFRC level, intracellular iron level and proliferation in glioma cells increased. Mechanistically, our data indicated that RP1-86C11.7 exacerbates the malignant behavior of glioma through the hsa-miR-144-3p/TFRC axis. RP1-86C11.7 may be a potential biomarker or target to treat glioma in the future.

胶质母细胞瘤 (GBM) 仍然是人类中枢神经系统最常见和最恶性肿瘤。越来越多的证据表明，具有高转铁蛋白受体 (TFRC) 表达的肿瘤细胞在生长方面表现出优势。长链非编码 RNA (lncRNA) 通过介导 microRNA (miRNA) 与胶质瘤进展相关。然而，GBM中TFRC、miRNA和lncRNA之间的潜在机制是有限的。在目前的研究中，我们确定了一种新的 lncRNA 诱导的信号传导机制，可调节 GBM 中的 TFRC 水平。胶质瘤细胞系中TFRC水平较高，TFRC表达升高促进了胶质瘤细胞的增殖和存活。进一步的研究表明，hsa-miR-144a-3p 与 TFRC mRNA 的 3'-UTR 结合并抑制其表达，从而阻止了胶质瘤细胞的恶性特性，如增殖和存活。我们还发现 lncRNA RP1-86C11.7 海绵 hsa-miR-144-3p 以抑制其在胶质瘤中的保护作用。神经胶质瘤细胞中 RP1-86C11.7 过表达提高了 TFRC 表达，增加了细胞内游离铁水平，并降低了致癌性，hsa-miR-144-3p 显着降低。相比之下，沉默 RP1-86C11.7 会上调 hsa-miR-144-3p 水平，导致 TFRC 表达降低并抑制胶质瘤进展。然而，沉默 RP1-86C11.7 的作用被同时 hsa-miR-144-3p 抑制剂治疗逆转：TFRC 水平、细胞内铁水平和胶质瘤细胞增殖增加。从机制上讲，我们的数据表明 RP1-86C11.7 通过 hsa-miR-144-3p/TFRC 轴加剧了胶质瘤的恶性行为。RP1-86C11。