Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710061, P.R. China.
Department of Geriatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.
Oncol Rep. 2023 Oct;50(4). doi: 10.3892/or.2023.8628. Epub 2023 Sep 15.
Dysregulation of long non‑coding RNAs (lncRNAs) is involved in the development of colorectal cancer (CRC). In the present study, the identification of muscle blind like splicing regulator 1 antisense RNA 1 (MBNL1‑AS1) lncRNA was reported. Firstly, Cell Counting Kit‑8, EdU and colony formation assays were uesed to explore the role of MBNL1‑AS1 in regulating the proliferation of CRC cells. According to TCGA database, it was found that MBNL1‑AS1 was correlated with microRNA (miR)‑29c‑3p and blood vessel epicardial substance (BVES) expression in CRC cells. Then, the regulation among MBNL1‑AS1, miR‑29C‑3P and BVES was detected by dual luciferase reporter assay and the function of MBNL1‑AS1/miR‑29C‑3P/BVES axis was explored by rescue assay. The results demonstrated that MBNL1‑AS1 expression was decreased in CRC and was associated with the size of tumors derived from patients with CRC. Functionally, the upregulation of MBNL1‑AS1 suppressed CRC cell proliferation and inhibited tumor growth , while knockdown of MBNL1‑AS1 expression caused the opposite effects. MBNL1‑AS1 expression correlated with BVES expression in CRC tissues and MBNL1‑AS1 enhanced the stability of BVES mRNA by functioning as a competing endogenous RNA to sponge miR‑29c‑3p; the latter directly targeted MBNL1‑AS1 and BVES mRNA 3'UTR. Collectively, the results indicated that MBNL1‑AS1 suppressed CRC cell proliferation by regulating miR‑29c‑3p/BVES signaling, suggesting that the MBNL1‑AS1/miR‑29c‑3p/BVES axis may be a potential therapeutic target for CRC.
长链非编码 RNA（lncRNA）的失调参与了结直肠癌（CRC）的发生发展。本研究报道了肌肉盲样剪接调节因子 1 反义 RNA 1（MBNL1-AS1）lncRNA 的鉴定。首先，使用细胞计数试剂盒-8、EdU 和集落形成实验探讨了 MBNL1-AS1 对 CRC 细胞增殖的调控作用。根据 TCGA 数据库，发现 MBNL1-AS1 与 CRC 细胞中的 microRNA（miR）-29c-3p 和血管心外膜物质（BVES）表达相关。然后，通过双荧光素酶报告基因实验检测 MBNL1-AS1、miR-29C-3P 和 BVES 之间的调控关系，并通过挽救实验探索 MBNL1-AS1/miR-29C-3P/BVES 轴的功能。结果表明，MBNL1-AS1 在 CRC 中表达下调，且与 CRC 患者肿瘤的大小相关。功能上，上调 MBNL1-AS1 抑制 CRC 细胞增殖和肿瘤生长，而下调 MBNL1-AS1 表达则产生相反的效果。MBNL1-AS1 表达与 CRC 组织中的 BVES 表达相关，MBNL1-AS1 通过作为竞争性内源性 RNA 来吸附 miR-29c-3p 增强 BVES mRNA 的稳定性；后者直接靶向 MBNL1-AS1 和 BVES mRNA 3'UTR。综上，结果表明 MBNL1-AS1 通过调节 miR-29c-3p/BVES 信号通路抑制 CRC 细胞增殖，提示 MBNL1-AS1/miR-29c-3p/BVES 轴可能是 CRC 的潜在治疗靶点。
