a Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University , Zhengzhou , Henan , China.
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):2536-2544. doi: 10.1080/21691401.2019.1621328.
Colon cancer, also known as colorectal carcinoma (CRC), remains to be one of the most mainsprings of cancer-produced deaths entire world. We planned to grab the role and possible biological cause of a long noncoding RNA, namely, small nucleolar RNA host gene 15 (SNHG15), in CRC. The mRNA level of SNHG15 in CRC tissues and cells was detected, followed by investigating the impacts of the depression of SNHG15 on CRC cell proliferation (viability and colony-forming), apoptosis, migration, and invasion. Moreover, the association between SNHG15 and miR-141 and the correlation between miR-141 and SIRT1 were also explored. Besides, the influences of dysregulated SNHG15 on the Wnt/β-catenin signal-related proteins were determined. SNHG15 was highly expressed in CRC tissues and cells. Depression of SNHG15 depressed proliferation, enhanced apoptosis, and repressed the migration and invasion of CRC cells. In addition, SNHG15 presented a downside tendency on regulating miR-141, and the miR-141 inhibitor dramatically changeover the impacts of SNHG15 depression on tumor growth and metastasis. Moreover, SIRT1 was verified as a functional target of miR-141 in CRC cells. Besides, the suppression of SNHG15 remarkably controlled activating the Wnt/β-catenin signals, which was reversed after inhibiting miR-141 at the same time. The investigated results in this research revealed that the increased expression of SNHG15 may enhance the process of CRC by acting as a ceRNA in regulating SIRT1 expression by sponging miR-141. Thus we propose that Wnt/β-catenin signals may be a downriver regulator in mediating the impacts of SNHG15 in CRC and SNHG15-miR-141-SIRT1 axis may pave a new sight in explaining the biological processes of CRC.
结肠癌，又称结直肠癌（CRC），仍然是全球癌症死亡的主要原因之一。我们计划研究长链非编码 RNA，即小核仁 RNA 宿主基因 15（SNHG15）在 CRC 中的作用和可能的生物学原因。检测了 CRC 组织和细胞中 SNHG15 的 mRNA 水平，然后研究了 SNHG15 抑制对 CRC 细胞增殖（活力和集落形成）、凋亡、迁移和侵袭的影响。此外，还探讨了 SNHG15 与 miR-141 的关系以及 miR-141 与 SIRT1 的相关性。此外，还确定了失调的 SNHG15 对 Wnt/β-catenin 信号相关蛋白的影响。SNHG15 在 CRC 组织和细胞中高表达。SNHG15 抑制降低了 CRC 细胞的增殖，增强了凋亡，并抑制了迁移和侵袭。此外，SNHG15 对 miR-141 的调节呈负相关趋势，miR-141 抑制剂显著改变了 SNHG15 抑制对肿瘤生长和转移的影响。此外，SIRT1 被验证为 CRC 细胞中 miR-141 的功能靶标。此外，SNHG15 的抑制显著控制了 Wnt/β-catenin 信号的激活，同时抑制 miR-141 后逆转了这一作用。本研究的研究结果表明，SNHG15 的表达增加可能通过作为 SIRT1 表达的 ceRNA 来调节 SIRT1 表达，从而增强 CRC 的发生过程，通过海绵吸附 miR-141。因此，我们提出 Wnt/β-catenin 信号可能是调节 SNHG15 在 CRC 中的作用的下游调节剂，SNHG15-miR-141-SIRT1 轴可能为解释 CRC 的生物学过程开辟新的视野。
