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Has_circ_0002360通过激活miR-762和调节PODXL表达促进肺腺癌进展。

Has_circ_0002360 promotes the progression of lung adenocarcinoma by activating miR-762 and regulating PODXL expression.

作者信息

Yan Yulan, Zhang Yao, He Yingjue, Bu Xuefeng

机构信息

Department of Respiratory Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.

Department of Tuberculosis, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

Transl Cancer Res. 2024 Aug 31;13(8):4172-4186. doi: 10.21037/tcr-24-279. Epub 2024 Aug 27.

DOI:10.21037/tcr-24-279
PMID:39262484
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11384312/
Abstract

BACKGROUND

Circular RNAs (circRNAs) have been found to be linked to cancer progression and metastasis, but there is not much known about their connection to lung adenocarcinoma (LAC). In the previous study reported by our group, has_circ_0002360 was highly expressed in LAC tissues. The goal of this study was to investigate the potential impact of has_circ_0002360 in LAC.

METHODS

Bioinformatics software, TargetScan, and miRanda were used to study the interactions of RNAs. Luciferase reporter assays further confirmed their relationship. The relative expression of has_circ_0002360 in 122 patients and four cell lines of the lung were obtained using real-time qualitative polymerase chain reaction (qRT-PCR). The target gene podocalyxin-like (PODXL) expression was confirmed by immunohistochemistry (IHC) in ten pairs of clinical samples. Then, cell counting kit-8 (CCK8), wound healing, and transwell experiments were applied to examine cell growth, migration, and infection-induced cell invasion. LAC cell lines were infected, and the process was monitored by examination of the related epithelial-mesenchymal transition (EMT) proteins.

RESULTS

The resulting data indicated that has_circ_0002360 and PODXL were overexpressed in LAC tissues, whereas miR-762 expression was repressed. The reduction of has_circ_0002360 or upregulation of miR-762 mitigated the proliferation, migration, invasion of LAC cells. Mechanistically, has_circ_0002360 upregulated PODXL expressions by targeting miR-762 to promote LAC progression.

CONCLUSIONS

In general, the has_circ_0002360/miR-762/PODXL axis affected the progress of LAC. The results of our study identified has_circ_0002360 as a novel oncogenic RNA in LAC.

摘要

背景

环状RNA（circRNAs）已被发现与癌症进展和转移有关，但它们与肺腺癌（LAC）的联系尚不清楚。在我们小组之前报道的研究中，has_circ_0002360在LAC组织中高表达。本研究的目的是探讨has_circ_0002360在LAC中的潜在影响。

方法

使用生物信息学软件TargetScan和miRanda研究RNA之间的相互作用。荧光素酶报告基因检测进一步证实了它们之间的关系。通过实时定量聚合酶链反应（qRT-PCR）获得122例患者和四种肺细胞系中has_circ_0002360的相对表达。通过免疫组织化学（IHC）在十对临床样本中确认靶基因多配体蛋白聚糖样蛋白（PODXL）的表达。然后，应用细胞计数试剂盒-8（CCK8）、伤口愈合和transwell实验检测细胞生长、迁移和感染诱导的细胞侵袭。对LAC细胞系进行感染，并通过检测相关上皮-间质转化（EMT）蛋白来监测这一过程。

结果

所得数据表明，has_circ_0002360和PODXL在LAC组织中过表达，而miR-762的表达受到抑制。has_circ_0002360的减少或miR-762的上调减轻了LAC细胞的增殖、迁移和侵袭。机制上，has_circ_0002360通过靶向miR-762上调PODXL表达，从而促进LAC进展。

结论

总体而言，has_circ_0002360/miR-762/PODXL轴影响了LAC的进展。我们的研究结果确定has_circ_0002360是LAC中一种新的致癌RNA。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/11384312/efa47d1155a9/tcr-13-08-4172-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/11384312/1b1fd1188c57/tcr-13-08-4172-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/11384312/47a8847bb2b4/tcr-13-08-4172-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/11384312/a8de5d02daa6/tcr-13-08-4172-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/11384312/ed831e7cda14/tcr-13-08-4172-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/11384312/921d322c6f31/tcr-13-08-4172-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/11384312/608c9efc0aaa/tcr-13-08-4172-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/11384312/9a78c6a66ab5/tcr-13-08-4172-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/11384312/efa47d1155a9/tcr-13-08-4172-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/11384312/1b1fd1188c57/tcr-13-08-4172-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/11384312/47a8847bb2b4/tcr-13-08-4172-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/11384312/a8de5d02daa6/tcr-13-08-4172-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/11384312/ed831e7cda14/tcr-13-08-4172-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/11384312/921d322c6f31/tcr-13-08-4172-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/11384312/608c9efc0aaa/tcr-13-08-4172-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/11384312/9a78c6a66ab5/tcr-13-08-4172-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/11384312/efa47d1155a9/tcr-13-08-4172-f8.jpg

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