Department of General Surgery, Shanghai Pudong New Area People Hospital affiliated to Shanghai University of Medicine & Health Sciences, Shanghai, China.
Department of Gastrointestinal Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
J Cell Mol Med. 2018 Nov;22(11):5565-5572. doi: 10.1111/jcmm.13830. Epub 2018 Aug 22.
Long non-coding RNAs (lncRNAs) have emerged as important regulators of cancer, including colorectal cancer (CRC). The exact expression pattern of long intergenic noncoding RNA 00312 (LINC00312) in CRC and its mechanisms of action have not been reported. Here, we found that LINC00312 is underexpressed in CRC tissues and cell lines. Functional experiments suggested that LINC00312 suppresses growth, migration and invasion of CRC cells in vitro and attenuates tumour proliferation and metastasis in vivo. Mechanistically, LINC00312 was found to regulate the malignancy of CRC cells by binding to miR-21 and by functioning as a tumour suppressor targeting PTEN. Overexpression of miR-21 or knockdown of PTEN attenuated the LINC00312-mediated inhibition of CRC cell proliferation and invasion. Taken together, our results elucidate the role of the LINC00312-miR-21-PTEN axis in CRC cell proliferation and tumour progression and may lead to new lncRNA-based diagnostics or therapeutics for CRC.
长非编码 RNA（lncRNAs）已成为癌症的重要调控因子，包括结直肠癌（CRC）。长基因间非编码 RNA 00312（LINC00312）在 CRC 中的确切表达模式及其作用机制尚未报道。在这里，我们发现 LINC00312 在 CRC 组织和细胞系中低表达。功能实验表明，LINC00312 在体外抑制 CRC 细胞的生长、迁移和侵袭，并在体内减弱肿瘤的增殖和转移。机制上，发现 LINC00312 通过与 miR-21 结合，并作为靶向 PTEN 的肿瘤抑制因子，调节 CRC 细胞的恶性程度。miR-21 的过表达或 PTEN 的敲低减弱了 LINC00312 对 CRC 细胞增殖和侵袭的抑制作用。总之，我们的研究结果阐明了 LINC00312-miR-21-PTEN 轴在 CRC 细胞增殖和肿瘤进展中的作用，并可能为 CRC 的新 lncRNA 诊断或治疗方法提供依据。
