Cai Ying, Zhu Chunlan, Wang Yanfei, Jiang Yiqian, Zhu Zhongxin
Department ofRespiratory, The First People's Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, China.
Department of Medical Oncology, The First People's Hospital of Xiaoshan District, Xiaoshan Affiliated Hospital of Wenzhou Medical University, Hangzhou, Zhejiang, China.
Front Genet. 2022 Aug 16;13:961668. doi: 10.3389/fgene.2022.961668. eCollection 2022.
Lung adenocarcinoma (LUAD) has a significant tendency to metastasize to the bone, with severe comorbidities. Recent studies have reported that circular RNAs (circRNAs) are involved in various cancer metastasis-related physiological cellular processes. However, their role in LUAD with bone metastasis (LUAD-BM) remains unknown. Bone metastasis (BM) circRNAs were identified using high-throughput sequencing and validated by quantitative reverse transcription-PCR (qRT-PCR). Bioinformatic analyses were used to predict the potential functions of the differentially expressed circRNAs. The effects of circ_0096442 on the growth and metastasis of A549 cells were detected in a co-culture system of A549 and bone marrow-derived cells. There were 598 (238 upregulated and 360 downregulated) 390 (187 upregulated and 203 downregulated) and 644 (336 upregulated and 308 downregulated) differentially expressed circRNAs between LUAD-BM and LUAD, LUAD-BM and healthy individuals, and LUAD and healthy individuals, respectively. These differentially expressed circRNAs play important roles in cellular components, biological processes, and molecular functions. Moreover, they map several pathways related to BM, including DNA repair, DNA damage, and osteoclast differentiation. The results validated by qRT-PCR for the five most dysregulated circRNAs are consistent with the sequencing data. Additionally, circ_0096442 was found to promote the growth and metastasis of LUAD in a bone microenvironment. Our findings provide a novel and important circRNA expression profile of LUAD-BM and suggest that circ_0096442 may be a biomarker for LUAD-BM.
肺腺癌（LUAD）有显著的骨转移倾向，并伴有严重的合并症。最近的研究报道，环状RNA（circRNA）参与各种与癌症转移相关的生理细胞过程。然而，它们在伴有骨转移的肺腺癌（LUAD-BM）中的作用仍不清楚。通过高通量测序鉴定骨转移（BM）circRNA，并通过定量逆转录PCR（qRT-PCR）进行验证。利用生物信息学分析预测差异表达circRNA的潜在功能。在A549细胞与骨髓来源细胞的共培养系统中检测circ_0096442对A549细胞生长和转移的影响。在LUAD-BM与LUAD、LUAD-BM与健康个体、LUAD与健康个体之间，分别有598个（238个上调和360个下调）、390个（187个上调和203个下调）和644个（336个上调和308个下调）差异表达的circRNA。这些差异表达的circRNA在细胞成分、生物学过程和分子功能中发挥重要作用。此外，它们涉及几个与骨转移相关的途径，包括DNA修复、DNA损伤和破骨细胞分化。对五个失调最严重的circRNA进行qRT-PCR验证的结果与测序数据一致。此外，发现circ_0096442在骨微环境中促进LUAD的生长和转移。我们的研究结果提供了一种新的、重要的LUAD-BM的circRNA表达谱，并表明circ_0096442可能是LUAD-BM的生物标志物。
