Department of Molecular Biology, Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Molecular Medicine, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
J Cell Physiol. 2020 Jul;235(7-8):5570-5589. doi: 10.1002/jcp.29488. Epub 2020 Feb 3.
Modulation of fatty acids metabolism is an appropriate strategy for starvation-induced death in tumor cancers. Colon cancer cells express a high level of acyl-CoA synthetase-5 (ACSL5), and as yet no therapeutic approach has been achieved. Herein, ACSL5-related microRNAs (miRNAs) were identified via TargetScan, and their impacts on ACSL5 and lipid content along with metabolic activity, cell cycle, migration, and invasion of colorectal cancer (CRC) cells were examined, and subsequently compared with transcriptome for better visualization of intracellular-signaling networks. In vivo analysis was performed using BALB/c mice xenograft model of CRC injected with target miRNA. Clinical significances were also evaluated in 80 CRC tumors and matched adjacent normal tissues. There was a reverse correlation between ACSL5 and miR-497-5p, which miR-497-5p overexpression modulated CRC cell proliferation and development. A similar observation was received from the in vivo examination in which intratumoral injection of miR-497-5p reversed the tumor growth in the CRC xenograft model. Downregulation of miR-497-5p correlated with tumor differentiation, tumor, node, and metastasis staging, lymph node metastasis, and poor survival in patients with CRC. These results suggested that miR-497-5p upregulation could be considered as a therapeutic strategy for modulation of lipid metabolism in colon cancer.
脂肪酸代谢的调节是诱导肿瘤细胞发生饥饿死亡的一种恰当策略。结肠癌细胞表达高水平的酰基辅酶 A 合成酶 5（ACSL5），但迄今为止尚未实现任何治疗方法。在此，通过 TargetScan 鉴定了与 ACSL5 相关的 microRNA（miRNA），并研究了它们对 ACSL5 和脂质含量以及代谢活性、细胞周期、迁移和侵袭的影响，随后与转录组进行比较，以便更好地可视化细胞内信号网络。使用注射靶向 miRNA 的 CRC 裸鼠异种移植模型进行体内分析。还在 80 个 CRC 肿瘤和匹配的相邻正常组织中评估了临床意义。ACSL5 与 miR-497-5p 呈负相关，miR-497-5p 的过表达调节了 CRC 细胞的增殖和发育。体内研究也得到了类似的观察结果，其中 miR-497-5p 的肿瘤内注射逆转了 CRC 异种移植模型中的肿瘤生长。miR-497-5p 的下调与肿瘤分化、肿瘤、淋巴结和转移分期、淋巴结转移以及 CRC 患者的不良生存相关。这些结果表明，miR-497-5p 的上调可以被认为是调节结肠癌脂质代谢的一种治疗策略。
