UKM Medical Molecular Biology Institute (UMBI), UKM Medical Center, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Cheras, 56000, Kuala Lumpur, Malaysia.
Department of Surgery, Faculty of Medicine, UKM Medical Center, Universiti Kebangsaan Malaysia, Jalan Yaacob Latiff, Cheras, 56000, Kuala Lumpur, Malaysia.
Clin Transl Oncol. 2018 Jun;20(6):775-784. doi: 10.1007/s12094-017-1788-x. Epub 2017 Nov 2.
Colorectal cancer (CRC) is one of the most widely diagnosed cancers in men and women worldwide. With the advancement of next-generation sequencing technologies, many studies have highlighted the involvement of long non-coding RNAs (lncRNAs) in cancer development. Growing evidence demonstrates that lncRNAs play crucial roles in regulating gene and protein expression and are involved in various cancers, including CRC. The field of lncRNAs is still relatively new and a lot of novel lncRNAs have been discovered, but their functional roles are yet to be elucidated. This study aims to characterize the expression and functional roles of a novel lncRNA in CRC.
Several methods were employed to assess the function of LOC285629 such as gene silencing, qPCR, proliferation assay, BrdU assay, transwell migration assay, ELISA and protein profiler.
Via in silico analyses, we identified significant downregulation of LOC285629, a novel lncRNA, across CRC stages. LOC285629 expression was significantly downregulated in advanced stages (Stage III and IV) compared to Stage I (Kruskal-Wallis Test; p = 0.0093). Further in-house validation showed that the expression of LOC285629 was upregulated in colorectal cancer tissues and cell lines compared to the normal counterparts, but was downregulated in advanced stages. By targeting LOC285629, the viability, proliferative abilities, invasiveness and resistance of colorectal cancer cells towards 5-fluorouracil were reduced. It was also discovered that LOC285629 may regulate cancer progression by targeting several different proteins, namely survivin, BCL-xL, progranulin, PDGF-AA, enolase 2 and p70S6 K.
Our findings suggest that LOC285629 may be further developed as a potential therapeutic target for CRC treatment.
结直肠癌（CRC）是全球男性和女性中最广泛诊断的癌症之一。随着下一代测序技术的进步，许多研究强调了长非编码 RNA（lncRNA）在癌症发展中的作用。越来越多的证据表明，lncRNA 在调节基因和蛋白质表达中发挥着关键作用，并参与包括 CRC 在内的各种癌症。lncRNA 领域仍然相对较新，许多新的 lncRNA 已经被发现，但它们的功能作用仍有待阐明。本研究旨在表征新型 lncRNA 在 CRC 中的表达和功能作用。
采用基因沉默、qPCR、增殖试验、BrdU 试验、Transwell 迁移试验、ELISA 和蛋白谱分析等多种方法评估 LOC285629 的功能。
通过计算机分析，我们发现新型 lncRNA LOC285629 在 CRC 各阶段均显著下调。与阶段 I（Kruskal-Wallis 检验；p=0.0093）相比，LOC285629 的表达在晚期（III 期和 IV 期）显著下调。进一步的内部验证表明，与正常对照相比，LOC285629 在结直肠癌细胞和组织中的表达上调，但在晚期阶段下调。通过靶向 LOC285629，结直肠癌细胞的活力、增殖能力、侵袭性和对 5-氟尿嘧啶的耐药性降低。还发现 LOC285629 可能通过靶向几种不同的蛋白质，即生存素、BCL-xL、颗粒蛋白、PDGF-AA、烯醇酶 2 和 p70S6K，来调节癌症的进展。
我们的研究结果表明，LOC285629 可能进一步开发为 CRC 治疗的潜在治疗靶点。
