Department of Neurosurgery, Zhangzhou Municipal Hospital of Fujian Province and Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, China.
Department of Nephrology, Zhangzhou Municipal Hospital of Fujian Province and Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, China.
Histol Histopathol. 2022 Jun;37(6):543-554. doi: 10.14670/HH-18-425. Epub 2022 Feb 1.
Increasing studies have found that long noncoding RNAs (lncRNAs) contribute to regulating tumor progression. This study explores the expression characteristics, effects, and related mechanisms of lncRNA IGF1R antisense imprinted non-protein coding RNA (IRAIN) in glioma.
Quantitative real-time PCR (qRT-PCR) was implemented to testify the IRAIN profile in glioma tissues and paracancerous tissues, and the link between the IRAIN level and the clinicopathological indicators of glioma was analyzed. IRAIN overexpression and knockdown cell models were constructed in glioma cells. Cell proliferation was verified by the colony formation experiment, while flow cytometry was implemented to monitor apoptosis. Transwell assay was performed to examine cell invasion and migration. Western blot (WB) was adopted to compare the profiles of the apoptosis-related proteins (Bax, Bcl2, and Caspase3) and IGF-1R-PI3K-NF-κB pathway.
IRAIN was down-regulated in glioma tissues (compared with adjacent normal tissues), and the low IRAIN expression was significantly linked with the larger tumor volume and higher pathological stages. Functionally, overexpressing IRAIN abated glioma cell proliferation, invasion, and migration, promoted apoptosis, and attenuated IGF-1R-PI3K-NF-κB expression and temozolomide (TMZ) resistance, which was also confirmed in the xenograft tumor experiment. The WB result showed that overexpressing IRAIN inactivated the IGF-1R-PI3K-NF-κB pathway. Additionally, the IGF-1R knockdown model was established in U251 cells. Si-IGF-1R induced cell proliferation inhibition, promoted cell death, and reduced cell migration and TMZ resistance, whereas Si-IGF-1R+IRAIN group showed no additional effects on glioma cells compared with the Si-IGF-1R group.
IRAIN repressed glioma development and TMZ resistance by inactivating the IGF-1R-PI3K-NF-κB axis.
越来越多的研究发现，长非编码 RNA（lncRNA）有助于调控肿瘤进展。本研究探讨了 lncRNA IGF1R 反义印记非蛋白编码 RNA（IRAIN）在神经胶质瘤中的表达特征、作用及相关机制。
采用实时定量 PCR（qRT-PCR）检测神经胶质瘤组织和癌旁组织中的 IRAIN 谱，并分析 IRAIN 水平与神经胶质瘤临床病理指标的关系。在神经胶质瘤细胞中构建 IRAIN 过表达和敲低细胞模型。通过集落形成实验验证细胞增殖，通过流式细胞术监测细胞凋亡。Transwell 实验检测细胞侵袭和迁移。采用 Western blot（WB）检测凋亡相关蛋白（Bax、Bcl2 和 Caspase3）和 IGF-1R-PI3K-NF-κB 通路的表达谱。
IRAIN 在神经胶质瘤组织中表达下调（与相邻正常组织相比），低 IRAIN 表达与肿瘤体积较大、病理分期较高显著相关。功能上，过表达 IRAIN 可抑制神经胶质瘤细胞的增殖、侵袭和迁移，促进凋亡，并减弱 IGF-1R-PI3K-NF-κB 的表达和替莫唑胺（TMZ）耐药性，这在异种移植瘤实验中也得到了证实。WB 结果表明，IRAIN 过表达可使 IGF-1R-PI3K-NF-κB 通路失活。此外，在 U251 细胞中建立了 IGF-1R 敲低模型。Si-IGF-1R 诱导细胞增殖抑制、促进细胞死亡、减少细胞迁移和 TMZ 耐药性，而 Si-IGF-1R+IRAIN 组与 Si-IGF-1R 组相比，对神经胶质瘤细胞没有额外作用。
IRAIN 通过使 IGF-1R-PI3K-NF-κB 轴失活，抑制神经胶质瘤的发展和 TMZ 耐药性。
