Department of Clinical Laboratory, Taizhou Central Hospital (Taizhou University Hospital), China.
Department of Respiratory Medicine, Taizhou Hospital of Wenzhou Medical University, China.
Tissue Cell. 2021 Oct;72:101535. doi: 10.1016/j.tice.2021.101535. Epub 2021 Mar 24.
LINC01089, a newly discovered long non-coding RNA (lncRNA), has been reported to inhibit the progression of various types of cancers. This study aimed to characterize LINC01089 in the pathogenesis of lung adenocarcinoma (LUAD). LINC01089 expression in LUAD tissues or/and cells and its association with the overall survival of LUAD patients was analyzed in The Cancer Genome Atlas (TCGA)-LUAD database, by qRT-PCR or by Kaplan-Meier's curve. Databases of StarBase, LncBase, and DEmiRNA were used to predict and confirm the interaction between LINC01089 and potential LINC01089-targeted microRNAs (miRNAs). The expressions of these miRNAs in LUAD tissues or/and cells were determined by qRT-PCR, and dual-luciferase reporter assay was performed to validate lncRNA-miRNA interaction. The expressions of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and Cleaved caspase-3 in LUAD cells were analyzed by Western blot. LINC01089 improved overall survival of LUAD patients and was low-expressed in LUAD. Upregulating LINC01089 expression reduced LUAD cell viability, inhibited colony formation, enhanced apoptosis, accompanied by downregulated Bcl-2 and miR-543 and upregulated Bax and Cleaved caspase-3. MiR-543 was determined as a target gene of LINC01089, and was high-expressed in LUAD tissues. Upregulating miR-543 expression induced the opposite effects to LINC01089 upregulation on these cellular biological behaviors and the expressions of Bcl-2, Bax and Cleaved caspase-3. Moreover, the effects of miR-543 upregulation and LINC01089 upregulation were mutually counteracted by each other. LINC01089 inhibited lung adenocarcinoma cell proliferation and promoted apoptosis via sponging miR-543.
LINC01089 是一种新发现的长链非编码 RNA（lncRNA），已被报道能抑制多种类型癌症的进展。本研究旨在探讨 LINC01089 在肺腺癌（LUAD）发病机制中的作用。通过 qRT-PCR 或 Kaplan-Meier 曲线分析癌症基因组图谱（TCGA）-LUAD 数据库中 LUAD 组织或/和细胞中的 LINC01089 表达情况及其与 LUAD 患者总生存期的关系。通过 StarBase、LncBase 和 DEmiRNA 数据库预测和验证 LINC01089 与潜在的 LINC01089 靶向 microRNAs（miRNAs）之间的相互作用。通过 qRT-PCR 测定这些 miRNAs 在 LUAD 组织或/和细胞中的表达，并通过双荧光素酶报告基因实验验证 lncRNA-miRNA 相互作用。通过 Western blot 分析 LUAD 细胞中 B 细胞淋巴瘤 2（Bcl-2）、Bcl-2 相关 X 蛋白（Bax）和Cleaved caspase-3 的表达。LINC01089 可改善 LUAD 患者的总生存期，且在 LUAD 中低表达。上调 LINC01089 表达可降低 LUAD 细胞活力，抑制集落形成，增强细胞凋亡，同时下调 Bcl-2 和 miR-543，上调 Bax 和 Cleaved caspase-3。miR-543 被确定为 LINC01089 的靶基因，在 LUAD 组织中高表达。上调 miR-543 表达可诱导与上调 LINC01089 表达相反的作用，对这些细胞生物学行为以及 Bcl-2、Bax 和 Cleaved caspase-3 的表达产生相反的作用。此外，上调 miR-543 表达和上调 LINC01089 表达的作用可相互抵消。LINC01089 通过海绵吸附 miR-543 抑制肺腺癌细胞增殖并促进凋亡。
