LncRNA SLCO4A1-AS1 modulates colon cancer stem cell properties by binding to miR-150-3p and positively regulating SLCO4A1.
LncRNA SLCO4A1-AS1 modulates colon cancer stem cell properties by binding to miR-150-3p and positively regulating SLCO4A1.
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DOI：
10.1038/s41374-021-00577-7
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发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Jiang B
中科院分区：
文献类型：
--
作者：
Wu K;Xu T;Song X;Shen J;Zheng S;Zhang L;Tao G;Jiang B
长链非编码RNA（lncRNA）在一系列不同的人类癌症中发挥重要作用。然而，lncRNA溶质载体有机阴离子转运蛋白家族成员4A 1-AS 1（SLCO 4A 1-AS 1）在结肠癌中的作用仍然是个谜。因此，我们的目的是探索SLCO 4A 1-AS 1在结肠癌干细胞中的特异性作用。采用基因芯片技术筛选结肠癌相关的lncRNA和mRNA差异表达，采用逆转录定量聚合酶链反应（RT-PCR）和Western blot技术检测结肠癌组织中SLCO 4A 1-AS 1和SLCO 4A 1的表达。采用双荧光素酶报告基因分析、RNA免疫沉淀和RNA pull-down技术验证SLCO 4A 1-AS 1、microRNA-150 - 3 p（miR-150- 3 p）和SLCO 4A 1之间的相互作用。此外，SLCO 4A 1-AS 1、miR-150- 3 p和/或SLCO 4A 1在结肠癌细胞中过表达或耗尽，以使用体外和体内测定来检测它们对结肠癌干细胞CD 133 + CD 44+细胞的迁移、侵袭、球体形成、凋亡和肿瘤发生能力的影响。筛选出SLCO 4A 1-AS 1和SLCO 4A 1作为结肠癌组织中差异表达的lncRNA和mRNA。SLCO 4A 1-AS 1被证实与miR-150- 3 p竞争性结合以提高SLCO 4A 1表达。此外，SLCO 4A 1-AS 1的敲低降低了SLCO 4A 1的表达，从而抑制了细胞的迁移、侵袭、球体形成和肿瘤发生能力，并增强了CD 133 + CD 44+细胞的凋亡。总的来说，这些发现提供了证据，证明耗尽SLCO 4A 1-AS 1竞争性结合miR-150- 3 p，其下调SLCO 4A 1表达，从而阻碍结肠癌进展。这项研究报告了长非编码RNA lncRNA SLCO 4A 1-AS 1调节结肠癌干细胞的特性。此外，SLCO 4A 1靶向miR-150- 3 p。LncRNA SLCO 4A 1-AS 1可以作为ceRNA吸附miR-150- 3 p，从而影响SLCO 4A 1的表达。在机制上，miR-150- 3 p可以下调SLCO 4A 1，从而抑制结肠癌干细胞的迁移、侵袭、球化和肿瘤形成。本研究为深入了解结肠癌的发病机制奠定了理论基础，并指出了新的治疗靶点。
Long non-coding RNAs (lncRNAs) play important roles in a range of different human cancers. However, the role of lncRNA solute carrier organic anion transporter family member 4A1-AS1 (SLCO4A1-AS1) in colon cancer remains enigmatic. Hence, we aimed to explore the specific role of SLCO4A1-AS1 in colon cancer stem cells. Colon cancer-related differentially expressed lncRNA and mRNA were screened using microarray-based analysis, and the expression of SLCO4A1-AS1 and SLCO4A1 in colon cancer tissues was determined using reverse transcription quantitative polymerase chain reaction and western blot analysis. The interaction among SLCO4A1-AS1, microRNA-150-3p (miR-150-3p) and SLCO4A1 was verified using dual-luciferase reporter assay, RNA immunoprecipitation and RNA pull-down. Moreover, SLCO4A1-AS1, miR-150-3p and/or SLCO4A1 were overexpressed or depleted in colon cancer cells to detect their effects on migration, invasion, sphere formation, apoptosis and tumorigenesis abilities of colon cancer stem CD133+CD44+ cells using both in vitro and in vivo assays. SLCO4A1-AS1 and SLCO4A1 were screened as the differentially expressed lncRNA and mRNA in colon cancer tissues. SLCO4A1-AS1 was confirmed to competitively bind to miR-150-3p to elevate SLCO4A1 expression. Moreover, knockdown of SLCO4A1-AS1 decreased SLCO4A1 expression, thus inhibiting cell migration, invasion, sphere formation, and tumorigenesis abilities and enhancing the apoptosis of CD133+CD44+ cells. Collectively, these findings provide evidence demonstrating that depleting SLCO4A1-AS1 competitively binds to miR-150-3p, which downregulates SLCO4A1 expression, thus hindering colon cancer progression. This study reports that long non-coding RNA lncRNA SLCO4A1-AS1 regulates the characteristics of colon cancer stem cells. Moreover, SLCO4A1 targets miR-150-3p. LncRNA SLCO4A1-AS1 can be used as ceRNA to adsorb miR-150-3p and thus affect the expression of SLCO4A1. Mechanistically, miR-150-3p can downregulate SLCO4A1, thereby inhibiting migration, invasion, spheroidization and tumor formation of colon cancer stem cells. This study lays a theoretical foundation for in-depth understanding of the pathogenesis of colon cancer and points to new therapeutic targets.
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