Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Cells. 2022 Aug 5;11(15):2421. doi: 10.3390/cells11152421.
The microRNA miR-187-3p plays antitumor roles in a variety of cancers. We and others have previously identified miR-187-3p as a potential tumor suppressor in colorectal cancer (CRC), but there are also reports revealing that high miR-187-3p levels are associated with poor prognosis among CRC patients. This study further investigated the clinicopathological significance of miR-187-3p in CRC.
MiR-187-3p levels in paired polyp/CRC/normal specimens or primary CRC/liver metastasis specimens were determined by qPCR, and correlated with the patient's clinicopathological and postoperative survival data. The clinical findings were validated using our validation cohort and data obtained from the TCGA or GEO databases. The functional effects of miR-187-3p were investigated through its overexpression in CRC cell lines.
MiR-187-3p was significantly repressed in colorectal polyps and CRC when compared to adjacent normal tissue. Overexpression of miR-187-3p in CRC cell lines impaired colony formation, cell migration, and invasion, and induced chemosensitivity. Clinical analysis revealed that despite miR-187-3p being repressed in CRC, high tumor miR-187-3p levels were positively correlated with tumor stage and disease recurrence. Further analysis showed that miR-187-3p levels were lower in metastatic specimens when compared to paired primary CRC, suggesting that high tumor miR-187-3p levels resulted from the dissemination of metastatic tumor cells. Tumor miR-187-3p levels were positively correlated with peripheral inflammation-related blood markers. Finally, SPRY1 was identified as a novel target gene of miR-187-3p, and was involved in miR-187-3p-impaired CRC metastasis.
This study demonstrated that in spite of its repression and role as a tumor suppressor in CRC, high levels of miR-187-3p in tumors were correlated with poor prognosis and higher levels of peripheral inflammation-related blood markers.
微小 RNA miR-187-3p 在多种癌症中发挥抗肿瘤作用。我们和其他人之前已经确定 miR-187-3p 是结直肠癌 (CRC) 中的潜在肿瘤抑制因子，但也有报道显示高 miR-187-3p 水平与 CRC 患者的预后不良相关。本研究进一步探讨了 miR-187-3p 在 CRC 中的临床病理意义。
通过 qPCR 确定配对息肉/CRC/正常标本或原发性 CRC/肝转移标本中的 miR-187-3p 水平，并将其与患者的临床病理和术后生存数据相关联。使用我们的验证队列和来自 TCGA 或 GEO 数据库的数据验证临床发现。通过在 CRC 细胞系中过表达 miR-187-3p 来研究其功能影响。
与相邻正常组织相比，miR-187-3p 在结直肠息肉和 CRC 中显著受抑制。在 CRC 细胞系中过表达 miR-187-3p 会损害集落形成、细胞迁移和侵袭，并诱导化学敏感性。临床分析表明，尽管 miR-187-3p 在 CRC 中受到抑制，但肿瘤 miR-187-3p 水平高与肿瘤分期和疾病复发呈正相关。进一步分析表明，与配对原发性 CRC 相比，转移标本中的 miR-187-3p 水平较低，表明高肿瘤 miR-187-3p 水平是转移性肿瘤细胞播散的结果。肿瘤 miR-187-3p 水平与外周炎症相关血液标志物呈正相关。最后，确定 SPRY1 是 miR-187-3p 的新靶基因，并参与 miR-187-3p 抑制的 CRC 转移。
本研究表明，尽管 miR-187-3p 在 CRC 中受到抑制并发挥肿瘤抑制因子的作用，但肿瘤中高 miR-187-3p 水平与预后不良和外周炎症相关血液标志物水平升高相关。
