Department of Stomatology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Pathology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Cell Oncol (Dordr). 2021 Jun;44(3):595-609. doi: 10.1007/s13402-021-00586-0. Epub 2021 Apr 2.
Long noncoding RNAs (lncRNAs) are emerging as key regulators in cancer initiation and progression. LINC01137 is a recently identified lncRNA of which the functional role in the development of oral squamous cell carcinoma (OSCC) has not been determined yet.
We analyzed the expression of LINC01137 using a microarray-based OSCC gene expression dataset (GSE31056), and validated the results obtained using RT-qPCR in 26 pairs of primary OSCC tumor tissues and adjacent non-tumor tissues. The proliferative and invasive effects of LINC01137 on OSCC cells were determined using CCK-8, colony formation and transwell assays, respectively. Targeted binding between miR-22-3p and LINC01137 was verified using a dual luciferase reporter assay.
We found that LINC01137 was significantly upregulated in primary OSCCs. LINC01137 knockdown inhibited OSCC cell proliferation, migration and invasion, whereas LINC01137 overexpression induced opposite effects. LINC01137 upregulation along with p53 inhibition enhanced the malignant transformation of oral cells. In addition, we found that miR-22-3p can directly target LINC01137 through interaction with a putative miR-22-3p-binding site present within the LINC01137 sequence. A significant negative correlation was observed between LINC01137 and miR-22-3p expression in primary OSCC specimens. Exogenous overexpression of miR-22-3p markedly reduced the endogenous expression level of LINC01137 in OSCC cells. Additional functional assays showed that miR-22-3p overexpression enhanced the inhibitory effect of siRNA-mediated LINC01137 silencing on OSCC cell proliferation, migration and invasion, whereas miR-22-3p inhibition had the opposite effect.
Our results indicate that LINC01137 functions as an oncogenic lncRNA in OSCC. miR-22-3p can directly target LINC01137 and negatively regulate its expression and function.
长链非编码 RNA（lncRNA）作为癌症发生和发展的关键调节因子而逐渐受到关注。LINC01137 是一种新发现的 lncRNA，但其在口腔鳞状细胞癌（OSCC）发展中的功能作用尚未确定。
我们使用基于微阵列的 OSCC 基因表达数据集（GSE31056）分析了 LINC01137 的表达情况，并使用 RT-qPCR 在 26 对原发性 OSCC 肿瘤组织和相邻非肿瘤组织中验证了结果。使用 CCK-8、集落形成和 Transwell 测定分别确定 LINC01137 对 OSCC 细胞的增殖和侵袭作用。使用双荧光素酶报告基因测定验证了 miR-22-3p 与 LINC01137 之间的靶向结合。
我们发现 LINC01137 在原发性 OSCC 中显著上调。LINC01137 敲低抑制了 OSCC 细胞的增殖、迁移和侵袭，而 LINC01137 过表达则诱导了相反的作用。LINC01137 的上调以及 p53 的抑制增强了口腔细胞的恶性转化。此外，我们发现 miR-22-3p 可以通过与 LINC01137 序列中存在的潜在 miR-22-3p 结合位点相互作用直接靶向 LINC01137。在原发性 OSCC 标本中观察到 LINC01137 与 miR-22-3p 表达之间存在显著负相关。外源性过表达 miR-22-3p 显著降低了 OSCC 细胞中内源性 LINC01137 的表达水平。额外的功能测定表明，miR-22-3p 过表达增强了 siRNA 介导的 LINC01137 沉默对 OSCC 细胞增殖、迁移和侵袭的抑制作用，而 miR-22-3p 抑制则产生相反的效果。
我们的结果表明，LINC01137 在 OSCC 中作为致癌 lncRNA 发挥作用。miR-22-3p 可以直接靶向 LINC01137 并负调控其表达和功能。
