Li Fengxia, Yang Jing, Li Yankun, Tan Zhenyu, Li Hui, Zhang Nong
Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.
Transl Oncol. 2023 Oct;36:101740. doi: 10.1016/j.tranon.2023.101740. Epub 2023 Jul 22.
Genetically abnormal fibroblasts are notably more prevalent in colorectal cancer (CRC) than in adjacent normal tissue, emphasizing their significance in driving the heterogeneity of the tumor microenvironment. Functioning as a significant regulatory gene in the context of fibrosis, FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) has exhibited abnormal expression in colorectal cancer and interstitial localization in our experiments. However, current research on the role of FENDRR in cancer has focused solely on its impact on cancer cells. Its crucial role in the tumor stroma is yet to be explored. The goal of this study was to understand the relationship between atypical FENDRR expression, its distinct localization, and genetically abnormal fibroblasts in CRC. We aimed to establish the function of FENDRR within the stromal compartment of patients through bioinformatics. Our study confirmed that FENDRR suppresses cancer-associated fibroblasts by inhibiting their activation and collagen generation in CRC. Furthermore, our findings suggest that low FENDRR expression indicates a poor prognosis. Therefore, we propose that FENDRR is a promising therapeutic target for future studies in CRC.
基因异常的成纤维细胞在结直肠癌（CRC）中比在相邻正常组织中明显更为普遍，这凸显了它们在驱动肿瘤微环境异质性方面的重要性。在纤维化背景下作为一个重要调节基因发挥作用的FOXF1相邻非编码发育调节RNA（FENDRR），在我们的实验中已显示出在结直肠癌中的异常表达和间质定位。然而，目前关于FENDRR在癌症中作用的研究仅集中在其对癌细胞的影响上。其在肿瘤基质中的关键作用尚待探索。本研究的目的是了解非典型FENDRR表达、其独特定位与CRC中基因异常的成纤维细胞之间的关系。我们旨在通过生物信息学确定FENDRR在患者基质区室中的功能。我们的研究证实，FENDRR通过抑制CRC中癌相关成纤维细胞的激活和胶原蛋白生成来抑制它们。此外，我们的研究结果表明FENDRR低表达预示着预后不良。因此，我们提出FENDRR是未来CRC研究中一个有前景的治疗靶点。
