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长链非编码RNA NR120519通过阻断KRT17促进下咽鳞状细胞癌的细胞增殖和迁移

LncRNA NR120519 Blocks KRT17 to Promote Cell Proliferation and Migration in Hypopharyngeal Squamous Carcinoma.

作者信息

Zhou Zheng, Zhang Gehou, Li Tieqi, Ai Jingang, Li Wei, Zeng Shiyu, Ye Maoyu, Liu Qian, Xiao Jian, Li Yunqiu, Tan Guolin, Zhang Xiaowei

机构信息

Department of Otolaryngology Head & Neck, Third Xiangya Hospital, Changsha 410013, China.

Department of Otolaryngology Head and Neck Surgery, Hunan Provincial People's Hospital, Changsha 410000, China.

出版信息

Cancers (Basel). 2023 Jan 18;15(3):603. doi: 10.3390/cancers15030603.

DOI:10.3390/cancers15030603
PMID:36765563
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9913485/
Abstract

BACKGROUND

Hypopharyngeal carcinoma is the worst type of head and neck squamous cell carcinoma. It is necessary to identify the key molecular targets related to the carcinogenesis and development of hypopharyngeal carcinoma.

METHODS

Differentially expressed lncRNAs in hypopharyngeal carcinoma were selected by microarray, and lncRNA-associated proteins were found by RIP assay. Colony formation, CCK-8, wound healing and Transwell assays were performed to detect the effects of lncRNA and its associated protein on cell proliferation and migration in vitro. Downstream pathways of lncRNA and its associated protein were detected by WB. Through a subcutaneous tumor model, the effects of lncRNA and its associated protein on cell proliferation were detected. The expressions of lncRNA and its associated protein in hypopharyngeal cancer tissues were detected by qRT-PCR and immunohistochemistry assays, respectively, and survival analyses were performed by Kaplan-Meier curve.

RESULTS

A total of 542 and 265 lncRNAs were upregulated and downregulated in microarrays, respectively. LncRNA NR120519 was upregulated and promoted cell proliferation and migration of hypopharyngeal carcinoma in vitro and cell proliferation in vivo. RIP and WB assays showed that KRT17 was associated with and blocked by NR120519.The silencing of KRT17 promoted cell proliferation and the migration of hypopharyngeal carcinoma in vitro and cell proliferation in vivo by activating the AKT/mTOR pathway and epithelial-mesenchymal transformation (EMT). Finally, the NR120519 high expression and KRT17 low expression groups showed shorter overall survival.

CONCLUSION

NR120519 activated the AKT/mTOR pathway and EMT by blocking KRT17 to promote cell proliferation and the migration of hypopharyngeal carcinoma.

摘要

背景

下咽癌是头颈部鳞状细胞癌中最严重的类型。有必要确定与下咽癌发生发展相关的关键分子靶点。

方法

通过微阵列筛选下咽癌中差异表达的lncRNAs，并通过RIP实验找到lncRNA相关蛋白。进行集落形成、CCK-8、伤口愈合和Transwell实验以检测lncRNA及其相关蛋白对体外细胞增殖和迁移的影响。通过WB检测lncRNA及其相关蛋白的下游通路。通过皮下肿瘤模型，检测lncRNA及其相关蛋白对细胞增殖的影响。分别通过qRT-PCR和免疫组化实验检测lncRNA及其相关蛋白在下咽癌组织中的表达，并通过Kaplan-Meier曲线进行生存分析。

结果

微阵列中分别有542个和265个lncRNAs上调和下调。lncRNA NR120519上调，并促进下咽癌细胞的体外增殖和迁移以及体内细胞增殖。RIP和WB实验表明KRT17与NR120519相关并被其阻断。KRT17的沉默通过激活AKT/mTOR通路和上皮-间质转化（EMT）促进下咽癌细胞的体外增殖和迁移以及体内细胞增殖。最后，NR120519高表达和KRT17低表达组的总生存期较短。

结论

NR120519通过阻断KRT17激活AKT/mTOR通路和EMT，从而促进下咽癌细胞增殖和迁移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/3cb258e41465/cancers-15-00603-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/8feac235a960/cancers-15-00603-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/542f995221c1/cancers-15-00603-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/e746c74bcfb5/cancers-15-00603-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/5ac89044fad1/cancers-15-00603-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/c22c3238608e/cancers-15-00603-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/518a7afff868/cancers-15-00603-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/4d3617ee2eaa/cancers-15-00603-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/a47453231249/cancers-15-00603-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/1aa5fa066c8c/cancers-15-00603-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/3cb258e41465/cancers-15-00603-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/8feac235a960/cancers-15-00603-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/542f995221c1/cancers-15-00603-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/e746c74bcfb5/cancers-15-00603-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/5ac89044fad1/cancers-15-00603-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/c22c3238608e/cancers-15-00603-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/518a7afff868/cancers-15-00603-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/4d3617ee2eaa/cancers-15-00603-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/a47453231249/cancers-15-00603-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/1aa5fa066c8c/cancers-15-00603-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e540/9913485/3cb258e41465/cancers-15-00603-g010.jpg

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