长链非编码 RNA BANCR 通过调节 Rab1A 信号通路促进口腔鳞状细胞癌的进展。
LncRNA BANCR promotes oral squamous cell carcinoma progression via regulating Rab1A signaling.
机构信息
Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China.
出版信息
J Oral Pathol Med. 2023 Sep;52(8):727-737. doi: 10.1111/jop.13463. Epub 2023 Jul 11.
BACKGROUND
Long non-coding RNA BRAF-activated non-protein coding RNA plays bidirectional roles in human cancers. However, function and molecular mechanism of BRAF-activated non-protein coding RNA in oral squamous cell carcinoma still need to clarify further.
METHODS
Long non-coding RNA microarray assay, in situ hybridization staining, clinicopathological data analysis were performed to investigate expression pattern of BRAF-activated non-protein coding RNA in oral squamous cell carcinoma tissue samples. Constructing ectopically expressed BRAF-activated non-protein coding RNA in oral squamous cell carcinoma cells via plasmids or siRNAs, then changeable abilities of proliferation and motility of these cells were observed in vitro and in vivo. RNA-protein pulldown, RNA immunoprecipitation, and bioinformatics analyses were performed to explore potential pathways involved in BRAF-activated non-protein coding RNA-based regulation of malignant progression in oral squamous cell carcinoma.
RESULTS
BRAF-activated non-protein coding RNA was identified upregulated in oral squamous cell carcinoma tissue and correlated with nodal metastasis and clinical severity of patients. Overexpressed BRAF-activated non-protein coding RNA increased percentage of 5-ethynyl-2'-deoxyuridine-positive cells, viability, migration, and invasion rates of oral squamous cell carcinoma cells, while silenced BRAF-activated non-protein coding RNA could observe weakened effects in vitro. Xenograft tumor formed by BRAF-activated non-protein coding RNA-overexpressed cells had bigger volume, faster growth rates, higher weight, and more Ki67 cells. Pulmonary metastasis induced by BRAF-activated non-protein coding RNA-silenced cells had fewer colony nodes, Ki67 cells, and CD31 blood vessels. Furthermore, BRAF-activated non-protein coding RNA was mainly localized in nucleus of oral squamous cell carcinoma cells and bound Ras-associated binding 1A. Silencing Ras-associated binding 1A could damage mobile ability and phosphorylation levels of nuclear factor-κB in oral squamous cell carcinoma cells induced by overexpressing BRAF-activated non-protein coding RNA. Opposite trend was also observed.
CONCLUSION
Acting as a promoter in oral squamous cell carcinoma metastasis, BRAF-activated non-protein coding RNA promotes oral squamous cell carcinoma cells proliferation and motility by regulating the BRAF-activated non-protein coding RNA/Ras-associated binding 1A complex, which activates nuclear factor-κB signaling pathway.
背景
长非编码 RNA BRAF 激活的非蛋白编码 RNA 在人类癌症中发挥双向作用。然而，BRAF 激活的非蛋白编码 RNA 在口腔鳞状细胞癌中的功能和分子机制仍需进一步阐明。
方法
通过长非编码 RNA 微阵列分析、原位杂交染色、临床病理数据分析，研究 BRAF 激活的非蛋白编码 RNA 在口腔鳞状细胞癌组织样本中的表达模式。通过质粒或 siRNA 在口腔鳞状细胞癌细胞中构建异位表达的 BRAF 激活的非蛋白编码 RNA，然后观察这些细胞在体外和体内的增殖和迁移能力的变化。进行 RNA-蛋白下拉、RNA 免疫沉淀和生物信息学分析，以探讨 BRAF 激活的非蛋白编码 RNA 调节口腔鳞状细胞癌恶性进展涉及的潜在途径。
结果
BRAF 激活的非蛋白编码 RNA 在口腔鳞状细胞癌组织中上调，并与淋巴结转移和患者临床严重程度相关。过表达 BRAF 激活的非蛋白编码 RNA 增加了口腔鳞状细胞癌细胞中 5-乙炔基-2'-脱氧尿苷阳性细胞的比例、细胞活力、迁移和侵袭率，而沉默 BRAF 激活的非蛋白编码 RNA 则可观察到体外减弱的效果。过表达 BRAF 激活的非蛋白编码 RNA 细胞形成的异种移植肿瘤体积更大、生长速度更快、重量更高、Ki67 细胞更多。沉默 BRAF 激活的非蛋白编码 RNA 细胞诱导的肺转移中，集落节点、Ki67 细胞和 CD31 血管较少。此外，BRAF 激活的非蛋白编码 RNA 主要定位于口腔鳞状细胞癌细胞的核内，并与 Ras 相关结合蛋白 1A 结合。沉默 Ras 相关结合蛋白 1A 可破坏过表达 BRAF 激活的非蛋白编码 RNA 诱导的口腔鳞状细胞癌细胞的迁移能力和核因子-κB 的磷酸化水平。相反的趋势也观察到。
结论
作为口腔鳞状细胞癌转移的促进剂，BRAF 激活的非蛋白编码 RNA 通过调节 BRAF 激活的非蛋白编码 RNA/Ras 相关结合蛋白 1A 复合物，激活核因子-κB 信号通路，促进口腔鳞状细胞癌细胞的增殖和迁移。
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