| Qian Zhong. Mechanism of lncRNA SNHG19 miR-299-5p MAPK6 signaling axis promoting metastasis of non-small cell lung cancer cells. Oncol Transl Med, 2022, 8: 247-258. |
| LncRNA SNHG19 miR-299-5p MAPK6信号转导轴促进非小细胞肺癌细胞转移的机制 |
| Mechanism of lncRNA SNHG19 miR-299-5p MAPK6 signaling axis promoting metastasis of non-small cell lung cancer cells |
| Received:September 05, 2022 Revised:October 22, 2022 |
| DOI：10.1007/s10330-022-0595-5 |
| 中文关键词: 长链非编码RNA小核仁RNA宿主基因19;微rna - 299 - 5 - p;非小细胞肺癌;转移 |
| 英文关键词: long noncoding RNA small nucleolar RNA host gene 19; MicroRNA-299-5p; non-small cell |
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| 中文摘要: |
| 目的探讨LncRNA小核仁RNA宿主基因19 (LncRNA SNHG19)/microrNA-299-5P (miR-299-5p) /丝裂原活化蛋白激酶6 (MAPK6)信号转导轴促进非小细胞肺癌(NSCLC)转移。方法分析lncrnas在非小细胞肺癌中的异常表达。从2021年8月到2022年8月，收集了50例手术切除的NSCLC和邻近组织样本。采用qRT-PCR检测LncRNA SNHG19、Mir-299-5p和MAPK6 mRNA表达水平。通过CCK-8法、克隆形成法、EdU法、scratch法、Transwell法、Western blotting法和体内异种移植实验研究LncRNA SNHG19、Mir-299-5p和MAPK6的功能。采用RNA荧光原位杂交(FISH)、RNA下拉实验、双荧光素酶报告基因实验和RNA共免疫沉淀实验探讨LncRNA SNHG19、miR-299-5p和MAPK6之间的作用机制。结果LncRNA SNHG19高表达与NSCLC患者不良预后、肿瘤大小、淋巴结转移及TNM分期相关(P < 0.05)。细胞功能实验显示，LncRNA SNHG19在体外和体内均能提高A549细胞的增殖、克隆形成、迁移和侵袭能力(均P < 0.05)，并能提高Vimentin和MAPK6的相对表达量(P < 0.05)。E-cadherin的相对表达量降低(P < 0.05)。LncRNA SNHG19可以与Mir-299-5p相互作用，调节MAPK6的表达水平。结论LncRNA SNHG19在非小细胞肺癌组织和细胞中表达上调，其高表达与肿瘤进展和不良生存有关。可作为Mir-299-5p的分子海绵，调节MAPK6的表达，促进A549细胞的增殖和转移。 |
| 英文摘要: |
| Objective The aim of this study was to explore the mechanism behind lncRNA small nucleolar RNA host
gene 19 (lncRNA SNHG19)/microrNA-299-5P (miR-299-5p)/mitogen-activated protein kinase 6 (MAPK6)
signaling axis promoting metastasis of non-small cell lung cancer (NSCLC).
Methods To analyze the abnormal expression of lncRNAs in NSCLC, 50 surgically resected NSCLC and
adjacent tissue samples were collected from August 2021 to August 2022. The mRNA expression levels of
lncRNA SNHG19, Mir-299-5p, and MAPK6 were detected by qRT-PCR. The functions of lncRNA SNHG19,
Mir-299-5p and MAPK6 were investigated by CCK-8, clone formation, EdU, scratch, Transwell western
blotting (WB)and in vivo xenograft assay. RNA fluorescence in-situ hybridization (FISH), RNA pull-down,
dual luciferase reporter, and RNA co-immunoprecipitation assays were used to explore the mechanism of
action between lncRNA SNHG19, miR-299-5p, and MAPK6.
Results High expression of lncRNA SNHG19 was correlated with poor prognosis, tumor size, lymph node
metastasis, and TNM stage in NSCLC patients (P < 0.05). Cell function experiments showed that lncRNA
SNHG19 could improve the proliferation, clone formation, migration, and invasion ability of A549 cells both
in vitro and in vivo (all P < 0.05) and increased the relative expression levels of vimentin and MAPK6 (P <
0.05). The relative expression level of E-cadherin was decreased (P < 0.05). lncRNA SNHG19 can interact
with Mir-299-5p and regulate the expression level of MAPK6.
Conclusion lncRNA SNHG19 is upregulated in NSCLC tissues and cells, and its high expression is
associated with tumor progression and poor survival. Moreover, it can act as a molecular sponge for Mir-
299-5p to regulate MAPK6 expression and promote the proliferation and metastasis of A549 cells. |
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