Zhou Xiaokun, Lv Liang, Zhang Zhongyi, Wei Shuyang, Zheng Tong
Department of Neurosurgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.
College of Pharmacy, Guilin Medical University, Guilin, Guangxi, China.
J Gene Med. 2020 Oct;22(10):e3235. doi: 10.1002/jgm.3235. Epub 2020 Jun 18.
Accumulating long noncoding RNAs (lncRNAs) have been recognized to participate in glioma development. Nevertheless, knowledge of the role of linc00294 in glioma remains incomplete.
Bioinformatics analysis predicted the differential expression of LINC00294 and neurofilament medium (NEFM) in tumors and normal tissues, as well as the binding between LINC00294 and miR-1278, miR-1278 and NEFM. Luciferase and RNA immunoprecipitation assays were used for the verification of interactions. The potential role of LINC00294 in glioma development was investigated using functional assays, singly and in parallel with its interplay with miR-1278 and NEFM. Cell counting kit-8 and EdU assays were applied to measure cellular proliferation, whereas the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method was employed to detect apoptosis.
A new lncRNA, LINC00294, was highly expressed in normal brain tissues. However, it was markedly down-regulated in GBM tissues and glioma cell lines. Overexpression of LINC00294 abates glioma cell proliferation but induces apoptosis. Meanwhile, tumor suppressor NEFM was revealed to be distinctly diminished in cancerous conditions and enhanced in glioma cells by LINC00294 up-regulation. Interactions of miR-1278 with LINC00294 or NEFM occur, and the expression of NEFM is up-regulated by LINC00294 through their competition with respect to binding to miR-1278. Finally, the rescue assays further confirmed that LINC00294 inhibits glioma cell proliferation by absorbing miR-1278 to enhance NEFM.
Collectively, our observations demonstrate the tumor-suppressive function of LINC00294 in glioma development by sponging miR-1278 and promoting NEFM, suggesting a potential use in therapy for glioma.
越来越多的长链非编码RNA（lncRNA）被认为参与了胶质瘤的发展。然而，关于linc00294在胶质瘤中的作用的了解仍不完整。
生物信息学分析预测了LINC00294和神经丝中链（NEFM）在肿瘤组织和正常组织中的差异表达，以及LINC00294与miR-1278、miR-1278与NEFM之间的结合。荧光素酶和RNA免疫沉淀试验用于验证相互作用。通过功能试验单独或与miR-1278和NEFM相互作用并行研究LINC00294在胶质瘤发展中的潜在作用。使用细胞计数试剂盒-8和EdU试验来测量细胞增殖，而采用末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）法检测细胞凋亡。
一种新的lncRNA，LINC00294，在正常脑组织中高表达。然而，它在胶质母细胞瘤组织和胶质瘤细胞系中明显下调。LINC00294的过表达抑制胶质瘤细胞增殖但诱导细胞凋亡。同时，肿瘤抑制因子NEFM在癌性条件下明显减少，而在胶质瘤细胞中通过LINC00294上调而增加。miR-1278与LINC00294或NEFM之间存在相互作用，并且LINC00294通过与miR-1278竞争结合而上调NEFM的表达。最后，挽救试验进一步证实LINC00294通过吸收miR-1278以增强NEFM来抑制胶质瘤细胞增殖。
总体而言，我们的观察结果表明LINC00294在胶质瘤发展中通过海绵吸附miR-1278和促进NEFM发挥肿瘤抑制功能，提示其在胶质瘤治疗中的潜在用途。
