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长链非编码RNA FAM222A-AS1负向调控miR-Let-7f以促进结直肠癌进展。

The Long Non-Coding RNA FAM222A-AS1 Negatively Modulates MiR-Let-7f to Promote Colorectal Cancer Progression.

作者信息

Song Mengmeng, Li Ye, Chen Zhewen, Zhang Jie, Yang Liuqing, Zhang Fan, Song Chunhua, Miao Mingyong, Chang Wenjun, Shi Hanping

机构信息

Department of Gastrointestinal Surgery/Clinical Nutrition, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, China.

Beijing International Science and Technology Cooperation Base for Cancer Metabolism and Nutrition, Beijing, China.

出版信息

Front Oncol. 2022 May 12;12:764621. doi: 10.3389/fonc.2022.764621. eCollection 2022.

DOI:10.3389/fonc.2022.764621
PMID:35646686
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9133450/
Abstract

Accumulating evidence indicates that lncRNAs are potential biomarkers and key regulators of tumor development and progression. The present study aimed to screen abnormal expression lncRNAs and investigate the mechanisms underlying the function in the progression of colorectal cancer (CRC). Potential CRC prognosis-associated dysregulated lncRNAs were screened and identified using bioinformatics analysis. Loss/gain-of-function experiments were performed to detect the biological roles of FAM222A-AS1 in CRC cell phenotypes and . The potential microRNAs that interact with FAM222A-AS1 were identified using online tools and were verified using qRT-PCR and luciferase reporter assay. The expression of FAM222A-AS1 is significantly upregulated in CRC tumor samples and cell lines. CRC patients with elevated FAM222A-AS1 expression in the tumor samples had unfavorable overall survival and disease-free survival. Silencing FAM222A-AS1 expression significantly inhibited CRC cell proliferation, migration, and invasion both and . Furthermore, FAM222A-AS1 was mainly distributed in the cytoplasm. It may directly bound to miR-let-7f and inhibit its expression and upregulate MYH9. In summary, FAM222A-AS1, as a novel oncogene in CRC, may promote the CRC progression by inhibiting miR-let-7f/MYH9 axis. The FAM222A-AS1/miR-let-7f/MYH9 signaling pathway may be a novel valuable target for inhibiting CRC.

摘要

越来越多的证据表明，长链非编码RNA（lncRNAs）是肿瘤发生发展的潜在生物标志物和关键调节因子。本研究旨在筛选异常表达的lncRNAs，并探讨其在结直肠癌（CRC）进展中发挥作用的机制。通过生物信息学分析筛选并鉴定了与CRC预后相关的潜在失调lncRNAs。进行功能缺失/获得实验以检测FAM222A-AS1在CRC细胞表型中的生物学作用。使用在线工具鉴定与FAM222A-AS1相互作用的潜在微小RNA，并通过qRT-PCR和荧光素酶报告基因检测进行验证。FAM222A-AS1在CRC肿瘤样本和细胞系中的表达显著上调。肿瘤样本中FAM222A-AS1表达升高的CRC患者总生存期和无病生存期均较差。沉默FAM222A-AS1表达显著抑制了CRC细胞的增殖、迁移和侵袭。此外，FAM222A-AS1主要分布在细胞质中。它可能直接与miR-let-7f结合并抑制其表达，上调MYH9。综上所述，FAM222A-AS1作为CRC中的一种新型癌基因，可能通过抑制miR-let-7f/MYH9轴促进CRC进展。FAM222A-AS1/miR-let-7f/MYH9信号通路可能是抑制CRC的一个新的有价值的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4092/9133450/662718c6c68a/fonc-12-764621-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4092/9133450/b554da8649c2/fonc-12-764621-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4092/9133450/60b41657f1c9/fonc-12-764621-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4092/9133450/f1033f2f0f24/fonc-12-764621-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4092/9133450/662718c6c68a/fonc-12-764621-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4092/9133450/b554da8649c2/fonc-12-764621-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4092/9133450/60b41657f1c9/fonc-12-764621-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4092/9133450/f1033f2f0f24/fonc-12-764621-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4092/9133450/662718c6c68a/fonc-12-764621-g004.jpg

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