General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, No. 68, Changle Road, Nanjing, 210006, China.
School of Medicine, Southeast University, Nanjing, 210009, China.
J Hematol Oncol. 2019 Jan 9;12(1):3. doi: 10.1186/s13045-018-0690-5.
Abnormal expression of long non-coding RNAs (lncRNAs) has been found in almost all human tumors, providing numerous potential diagnostic biomarkers, prognostic biomarkers, and therapeutic targets.
We analyzed RNA sequencing data to explore abnormally expressed lncRNAs in colorectal cancer (CRC). The functions of small nucleolar RNA host gene 6 (SNHG6) were investigated through in vitro and in vivo assays (CCK-8 assay, colony formation assay, flow cytometry assay, EdU assay, wound healing assay, transwell assay, and xenograft model). The mechanism of action of SNHG6 was explored through bioinformatics, RNA fluorescence in situ hybridization, luciferase reporter assay, RNA pull-down assay, chromatin immunoprecipitation assay, and RNA immunoprecipitation assay.
We identified aberrantly expressed lncRNAs in CRC. We found that elevated SNHG6 expression was associated with poor prognosis and CRC progression. We also demonstrated that the high SNHG6 expression was partly due to DNA copy number gains and SP1 induction. Functional studies showed that SNHG6 promoted CRC cell growth, migration, and invasion both in vitro and in vivo. Mechanistically, we found that SNHG6 expressed predominantly in the cytoplasm. SNHG6 could interact with miR-26a, miR-26b, and miR-214 and regulate their common target EZH2.
Our study elucidated that SNHG6 acted as an oncogene in CRC, which might serve as a novel target for CRC diagnosis and therapy.
异常表达的长非编码 RNA（lncRNA）几乎存在于所有人类肿瘤中，为诊断标志物、预后标志物和治疗靶点提供了大量潜在的候选分子。
我们通过 RNA 测序数据分析，探讨结直肠癌（CRC）中异常表达的 lncRNA。通过体外和体内实验（CCK-8 实验、集落形成实验、流式细胞术实验、EdU 实验、划痕愈合实验、Transwell 实验和异种移植模型）研究小核仁 RNA 宿主基因 6（SNHG6）的功能。通过生物信息学、RNA 荧光原位杂交、荧光素酶报告基因检测、RNA 下拉实验、染色质免疫沉淀实验和 RNA 免疫沉淀实验探讨 SNHG6 的作用机制。
我们鉴定了 CRC 中异常表达的 lncRNA。我们发现，SNHG6 表达升高与预后不良和 CRC 进展有关。我们还表明，SNHG6 的高表达部分归因于 DNA 拷贝数增加和 SP1 诱导。功能研究表明，SNHG6 在体外和体内均促进 CRC 细胞的生长、迁移和侵袭。机制研究表明，SNHG6 主要在细胞质中表达。SNHG6 可以与 miR-26a、miR-26b 和 miR-214 相互作用，并调节它们的共同靶基因 EZH2。
本研究阐明了 SNHG6 在 CRC 中作为癌基因的作用，可能为 CRC 的诊断和治疗提供新的靶点。
