A Novel Long Non-Coding RNA lnc030 Maintains Breast Cancer Stem Cell Stemness by Stabilizing SQLE mRNA and Increasing Cholesterol Synthesis.
A Novel Long Non-Coding RNA lnc030 Maintains Breast Cancer Stem Cell Stemness by Stabilizing SQLE mRNA and Increasing Cholesterol Synthesis.
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一种新型长非编码 RNA lnc030 通过稳定 SQLE mRNA 和增加胆固醇合成来维持乳腺癌干细胞干细胞性。
DOI：
10.1002/advs.202002232
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发表时间：
2021-01
期刊：
影响因子：
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通讯作者：
Liu M
中科院分区：
文献类型：
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作者：
Qin Y;Hou Y;Liu S;Zhu P;Wan X;Zhao M;Peng M;Zeng H;Li Q;Jin T;Cui X;Liu M
癌症干细胞（CSC）被认为是癌症转移和复发（CSC）的根源，部分原因是它们的自我更新和耐药性。然而，CSC干性调节的潜在机制知之甚少。最近，越来越多的证据表明，长链非编码RNA（lncRNA）是包括乳腺癌在内的各种恶性肿瘤中癌细胞功能的关键调节因子，但lncRNA如何调节乳腺癌干细胞（BCSC）的功能仍有待确定。在此，使用lncRNA/mRNA微阵列测定，鉴定出一种新型lncRNA（命名为lnc 030），其在体外和体内BCSC中高度表达，作为维持BCSC干性和促进肿瘤发生的关键调节因子。在机制上，lnc 030与聚（rC）结合蛋白2（PCBP 2）合作以稳定角鲨烯环氧酶（SQLE）mRNA，从而导致胆固醇合成的增加。增加的胆固醇反过来激活PI 3 K/Akt信号传导，其控制BCSC干性。总之，这些发现证明了一种新的、基于lnc 030的调节BCSC胆固醇合成和干性特性的机制。lnc 030-SQLE-胆固醇合成途径可能作为BCSC消除和乳腺癌治疗的有效治疗靶点。Lnc 030是一种新的lncRNA，在BCSC中高度表达，并在维持BCSC干性和肿瘤发生中起关键调节作用。Lnc 030与PCBP 2合作以稳定SQLE mRNA，导致胆固醇增加，从而激活PI 3 K/Akt信号传导以控制BCSC干性。lnc 030-SQLE-胆固醇合成途径可能作为BCSC消除和乳腺癌治疗的有效治疗靶点。
Cancer stem cells (CSCs) are considered the roots of cancer metastasis and recurrence (CSCs), due in part to their self‐renewal and therapy resistance properties. However, the underlying mechanisms for the regulation of CSC stemness are poorly understood. Recently, increasing evidence shows that long non‐coding RNAs (lncRNAs) are critical regulators for cancer cell function in various malignancies including breast cancer, but how lncRNAs regulate the function of breast cancer stem cells (BCSCs) remains to be determined. Herein, using lncRNA/mRNA microarray assays, a novel lncRNA (named lnc030) is identified, which is highly expressed in BCSCs in vitro and in vivo, as a pivotal regulator in maintaining BCSC stemness and promoting tumorigenesis. Mechanistically, lnc030 cooperates with poly(rC) binding protein 2(PCBP2) to stabilize squalene epoxidase (SQLE) mRNA, resulting in an increase of cholesterol synthesis. The increased cholesterol in turn actives PI3K/Akt signaling, which governs BCSC stemness. In summary, these findings demonstrate that a new, lnc030‐based mechanism for regulating cholesterol synthesis and stemness properties of BCSCs. The lnc030‐SQLE‐cholesterol synthesis pathway may serve as an effective therapeutic target for BCSC elimination and breast cancer treatment. Lnc030, a novel lncRNA, is highly expressed in BCSCs and acts as a pivotal regulator in maintaining BCSC stemness and tumorigenesis. Lnc030 cooperates with PCBP2 to stabilize SQLE mRNA, resulting in an increased cholesterol which actives PI3K/Akt signaling in governing BCSC stemness. The lnc030‐SQLE‐cholesterol synthesis pathway may serve as an effective therapeutic target for BCSC elimination and breast cancer treatment.