Wei Wei, Xu Teng, Zhang Ying, Huang Yong, Wang Xiang
Department of Cardiothoracic Surgery, Jinling Hospital, Nanjing University School of Medicine, Jiangsu, 210002, China.
Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Jiangsu, 221000, China.
Discov Oncol. 2022 May 30;13(1):41. doi: 10.1007/s12672-022-00501-5.
Long noncoding RNAs (lncRNAs) exert crucial biological functions by regulating miRNAs, which are implicated in cancer progression and tumorigenesis. A previous study has indicated that lncRNA linc02544 expression is upregulated in lung adenocarcinoma, whereas, the role of linc02544 in LUSC is elusive.
The differential linc02544 expression in LUSC tissues and adjacent non-tumor tissues were evaluated with RT-qPCR. Kaplan-Meier curve was conducted to evaluate the clinical prognostic significance of linc02544. Then cellular experiments were performed to assess the influence of linc02544 in LUSC proliferation, invasion, and migration, and a western blot assay was used to measure the metastasis-related protein levels. The downstream miRNAs were verified using the LncBase Experimental v.2 database and dual-luciferase reporter assay.
Linc02544 was overexpressed in LUSC tissues from positive lymph node metastasis-positive and TNM high-stage patients. Low linc02544 expression was associated with a longer survival rate. Downregulation of linc02544 by si-linc02544 restrained cell growth capacities, migration, and invasion abilities. Expression of MMP-2, MMP-9, and vimentin was decreased while E-cadherin was increased in si-linc02544 cells compared with that in untreated cells. Mechanistically, we identified that linc02544 acted as a sponge of miR-138-5p, which expression had a negative correlation. E2F3 was a potential target of miR-138-5p, CONCLUSIONS: Notably, high linc02544 expression was associated with severe clinical parameters and was a putative prognostic predictor for patients with LUSC. Downregulation of linc02544 may weaken the LUSC cell proliferation, migration, and invasion by regulating miR-138-5p/E2F3, which maybe serve as a biomarker for the prognosis and target treatment of LUSC.
长链非编码RNA(lncRNAs)通过调控微小RNA(miRNAs)发挥关键生物学功能,而miRNAs与癌症进展和肿瘤发生有关。先前的一项研究表明,lncRNA linc02544在肺腺癌中表达上调,然而,linc02544在肺鳞状细胞癌(LUSC)中的作用尚不清楚。
采用逆转录定量聚合酶链反应(RT-qPCR)评估LUSC组织和癌旁非肿瘤组织中linc02544的差异表达。绘制Kaplan-Meier曲线以评估linc02544的临床预后意义。随后进行细胞实验以评估linc02544对LUSC增殖、侵袭和迁移的影响,并使用蛋白质免疫印迹法检测转移相关蛋白水平。利用LncBase Experimental v.2数据库和双荧光素酶报告基因检测验证下游miRNAs。
linc02544在伴有阳性淋巴结转移和TNM高分期的LUSC组织中过表达。linc02544低表达与更长的生存率相关。与未处理细胞相比,小干扰RNA(si-linc02544)下调linc02544可抑制细胞生长能力、迁移和侵袭能力。si-linc02544处理的细胞中基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)和波形蛋白的表达降低,而E-钙黏蛋白的表达增加。机制上,我们发现linc02544作为miR-138-5p的海绵,二者表达呈负相关。E2F3是miR-138-5p的潜在靶标。
值得注意的是,linc02544高表达与严重的临床参数相关,是LUSC患者的一个潜在预后预测指标。下调linc02544可能通过调控miR-138-5p/E2F3减弱LUSC细胞的增殖、迁移和侵袭能力,这可能作为LUSC预后和靶向治疗的生物标志物。