Long non-coding RNA CASC9 promotes tumor progression in oral squamous cell carcinoma by regulating microRNA-545-3p/laminin subunit gamma 2

Long non-coding RNA (lncRNA) CASC9 is reported to be a tumor promoter in oral cancer, but its mechanism in oral squamous cell carcinoma (OSCC) has not been fully explored. Our study aimed to identify the interaction between lncRNA CASC9, microRNA-545-3p (miR-545-3p), and laminin subunit gamma 2 (LAMC2) in OSCC cells. Our study confirmed that lncRNA CASC9 and LAMC2 were upregulated in OSCC, whereas miR-545-3p expression was reduced. After performing a series of cell functional experiments, it was found that knockdown of lncRNA CASC9 or LAMC2 resulted in the inhibition of proliferation, colony formation, and migration of OSCC cells, but their negative effects could be partly impaired by the miR-545-3p inhibitor. In addition, we proved for the first time that lncRNA CASC9 can sponge miR-545-3p to upregulate LAMC2. In conclusion, our study revealed that lncRNA CASC9 promotes the malignancy of OSCC cells by sponging miR-545-3p to enhance LAMC2 expression, implying that lncRNA CASC9/miR-545-3p/LAMC2 may be an intervention approach in OSCC therapy.

已有研究表明，长链非编码RNA（long non-coding RNA，lncRNA）CASC9在口腔癌中发挥肿瘤促进因子的作用，但该分子在口腔鳞状细胞癌（oral squamous cell carcinoma，OSCC）中的具体作用机制尚未完全阐明。本研究旨在明确长链非编码RNA CASC9、微小RNA-545-3p（microRNA-545-3p，miR-545-3p）与层粘连蛋白亚基γ2（laminin subunit gamma 2，LAMC2）在口腔鳞状细胞癌细胞中的相互作用关系。本研究证实，在口腔鳞状细胞癌组织及细胞中，长链非编码RNA CASC9与层粘连蛋白亚基γ2（LAMC2）的表达均显著上调，而微小RNA-545-3p（miR-545-3p）的表达水平则显著降低。通过一系列细胞功能实验，本研究发现：敲低长链非编码RNA CASC9或层粘连蛋白亚基γ2（LAMC2）的表达可显著抑制口腔鳞状细胞癌细胞的增殖、集落形成及迁移能力，而该抑制效应可被miR-545-3p抑制剂部分逆转。此外，本研究首次证实，长链非编码RNA CASC9可通过海绵吸附作用靶向结合miR-545-3p，从而上调LAMC2的表达。综上，本研究揭示了长链非编码RNA CASC9通过海绵吸附miR-545-3p、上调LAMC2的表达，进而促进口腔鳞状细胞癌细胞的恶性表型，提示CASC9/miR-545-3p/LAMC2调控轴有望成为口腔鳞状细胞癌治疗的潜在干预靶点。