Wang Linxuan, Jin Wenjing, Wu Xiaochi, Liu Yuan, Gu Wenchao
Department of Respiratory and Critical Care Medicine, Shanghai Pudong New Area People's Hospital, Shanghai, China.
Histol Histopathol. 2023 Jan;38(1):73-89. doi: 10.14670/HH-18-498. Epub 2022 Jul 22.
CircRNAs function as pivotal molecules to regulate the malignant development of lung cancer. This study was designed to research the functional role and how it acted in lung cancer progression.
Circ_0000520, microRNA-512-5p (miR-512-5p) and Breast cancer-overexpressed gene 1 (KIAA0100) levels were measured through reverse transcription-quantitative polymerase chain reaction assay. Cell Counting Kit-8 assay and EdU assay were used to examine cell proliferation. Cell cycle and apoptosis were evaluated via flow cytometry. The protein levels were determined using western blot. Cell migration and invasion were assessed by wound healing assay and transwell assay. The circ_0000520 function in vivo was explored by tumor xenograft assay. The molecular interaction was analyzed via Dual-luciferase reporter assay.
Circ_0000520 was obviously upregulated in lung cancer tissues and cells. Silence of circ_0000520 inhibited proliferation, cell cycle progression, migration, invasion and angiogenesis but promoted cell apoptosis. Circ_0000520 downregulation reduced tumor growth of lung cancer in vivo. Circ_0000520 served as a miR-512-5p sponge. The oncogenic function of circ_0000520 was partly achieved by sponging miR-512-5p in lung cancer. KIAA0100 was a target of miR-512-5p and miR-512-5p inhibited the malignant behaviors of lung cancer cells via downregulating KIAA0100. Circ_0000520 targeted miR-512-5p to regulate the level of KIAA0100.
All these data demonstrated that circ_0000520 was able to drive the progression of lung cancer via the mediation of miR-512-5p/KIAA0100 axis. Circ_0000520 might be a potential biomarker for lung cancer.
环状RNA（circRNAs）作为关键分子参与调控肺癌的恶性发展。本研究旨在探究其功能作用以及在肺癌进展过程中的作用机制。
采用逆转录-定量聚合酶链反应检测环状RNA_0000520（circ_0000520）、微小RNA-512-5p（miR-512-5p）和乳腺癌过表达基因1（KIAA0100）的水平。使用细胞计数试剂盒-8法和EdU法检测细胞增殖。通过流式细胞术评估细胞周期和细胞凋亡。采用蛋白质免疫印迹法测定蛋白水平。通过伤口愈合实验和Transwell实验评估细胞迁移和侵袭能力。通过肿瘤异种移植实验探究circ_0000520在体内的功能。利用双荧光素酶报告基因实验分析分子间相互作用。
circ_0000520在肺癌组织和细胞中显著上调。沉默circ_0000520可抑制细胞增殖、细胞周期进程、迁移、侵袭和血管生成，但可促进细胞凋亡。circ_0000520表达下调可降低肺癌在体内的肿瘤生长。circ_0000520可作为miR-512-5p的海绵。circ_0000520在肺癌中的致癌功能部分是通过吸附miR-512-5p实现的。KIAA0100是miR-512-5p的靶标，miR-512-5p通过下调KIAA0100抑制肺癌细胞的恶性行为。circ_0000520靶向miR-512-5p来调节KIAA0100的水平。
所有这些数据表明，circ_0000520能够通过miR-512-5p/KIAA0100轴介导肺癌进展。circ_0000520可能是肺癌的潜在生物标志物。
