Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China.
Cancer Lett. 2024 Nov 1;604:217217. doi: 10.1016/j.canlet.2024.217217. Epub 2024 Sep 2.
Metastasis continues to negatively impact individuals diagnosed with colorectal cancer (CRC). Research has revealed the important role of long noncoding RNAs (lncRNAs) in CRC metastasis, but the underlying mechanisms remain unclear. Here, we revealed that the lncRNA small nucleolar RNA host gene 1 (SNHG1) is expressed at higher levels in metastatic CRC tissues than in primary CRC tissues, and that high lncRNA SNHG1 expression indicates poor patient outcomes. We found that lncRNA SNHG1 promotes the migration and invasion of tumor cells both in vivo and in vitro. Moreover, lncRNA SNHG1 increases serpin family A member 3 (SERPINA3) mRNA stability by interacting with the heterogeneous nuclear ribonucleoprotein D (HNRNPD) protein, and subsequently upregulates SERPINA3 expression. Moreover, HNRNPD and SERPINA3 reversed the effects of lncRNA SNHG1 knockdown on CRC cell metastasis. In conclusion, we report that the lncRNA SNHG1 recruits HNRNPD, in turn upregulating SERPINA3 expression and ultimately facilitating CRC cell migration and invasion. Targeting the lncRNA SNHG1/HNRNPD/SERPINA3 signaling pathway might be a therapeutic option for preventing CRC metastasis.
转移继续对被诊断患有结直肠癌 (CRC) 的个体产生负面影响。研究揭示了长非编码 RNA (lncRNA) 在 CRC 转移中的重要作用，但潜在机制仍不清楚。在这里，我们揭示了 lncRNA 小核仁 RNA 宿主基因 1 (SNHG1) 在转移性 CRC 组织中的表达水平高于原发性 CRC 组织，并且高 lncRNA SNHG1 表达表明患者预后不良。我们发现 lncRNA SNHG1 促进肿瘤细胞在体内和体外的迁移和侵袭。此外，lncRNA SNHG1 通过与异质核核糖核蛋白 D (HNRNPD) 蛋白相互作用增加丝氨酸蛋白酶抑制剂家族 A 成员 3 (SERPINA3) mRNA 的稳定性，随后上调 SERPINA3 表达。此外，HNRNPD 和 SERPINA3 逆转了 lncRNA SNHG1 敲低对 CRC 细胞转移的影响。总之，我们报告 lncRNA SNHG1 招募 HNRNPD，进而上调 SERPINA3 表达，最终促进 CRC 细胞迁移和侵袭。靶向 lncRNA SNHG1/HNRNPD/SERPINA3 信号通路可能是预防 CRC 转移的一种治疗选择。
