The State Key Laboratory of Pharmaceutical Biotechnology and Central Laboratory of Stomatology Nanjing of Stomatological Hospital, Division of Immunology, Medical School, Nanjing University, China.
State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, China.
Mol Oncol. 2022 Feb;16(3):780-794. doi: 10.1002/1878-0261.12935. Epub 2021 Jun 10.
Cancer-associated fibroblasts (CAF) are the most abundant stromal cells in tumor and exert a pro-tumoral effect in cancer progression. Numerous evidence shows long non-coding RNA (lncRNA) abnormally regulates gene expression in various cancers. However, little is known about the role of lncRNA in the interaction between CAF and cancer cells. Here, we first identify an uncharacterized lncRNA, LOC100506114, which is significantly upregulated in CAF and is involved in the functional transformation of normal fibroblasts (NF) and CAF. Expression of LOC100506114 enhances the expression of fibroblast activation protein alpha and α-smooth muscle actin in NF and promotes malignant characteristics of NF and CAF in vivo and in vitro. The profile of gene co-expression analysis shows that growth differentiation factor 10 (GDF10) is positively correlated with the expression of LOC100506114. CAF promote stromal fibroblast activation and the proliferation and migration of tumor cells by secreting GDF10. Our data demonstrate that lncRNA plays a critical role in the interplay of stromal fibroblasts and tumor cells in oral squamous cell carcinoma.
癌症相关成纤维细胞（CAF）是肿瘤中最丰富的基质细胞，在癌症进展中发挥促肿瘤作用。大量证据表明，长非编码 RNA（lncRNA）在各种癌症中异常调节基因表达。然而，lncRNA 在 CAF 与癌细胞相互作用中的作用知之甚少。在这里，我们首先鉴定了一种未被表征的 lncRNA，LOC100506114，它在 CAF 中显著上调，并参与正常成纤维细胞（NF）和 CAF 的功能转化。LOC100506114 的表达增强了 NF 中成纤维细胞活化蛋白α和α-平滑肌肌动蛋白的表达，并促进了 NF 和 CAF 在体内和体外的恶性特征。基因共表达分析的特征表明，生长分化因子 10（GDF10）与 LOC100506114 的表达呈正相关。CAF 通过分泌 GDF10 促进基质成纤维细胞的激活以及肿瘤细胞的增殖和迁移。我们的数据表明，lncRNA 在口腔鳞状细胞癌中基质成纤维细胞和肿瘤细胞相互作用中起着关键作用。
