LncRNA HOTAIR Promotes Cancer Stem-Like Cells Properties by Sponging miR-34a to Activate the JAK2/STAT3 Pathway in Pancreatic Ductal Adenocarcinoma.
LncRNA HOTAIR Promotes Cancer Stem-Like Cells Properties by Sponging miR-34a to Activate the JAK2/STAT3 Pathway in Pancreatic Ductal Adenocarcinoma.
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长链非编码RNA HOTAIR通过吸附微小RNA-34a激活JAK2/STAT3信号通路促进胰腺导管腺癌中癌干细胞样特性 。
DOI：
10.2147/ott.s286666
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发表时间：
2021
影响因子：
4
通讯作者：
Jin Y
中科院分区：
文献类型：
--
作者：
Deng S;Wang J;Zhang L;Li J;Jin Y
胰腺导管腺癌（PDAC）干细胞（CSCs）在PDAC的发生、发展和复发中起着重要作用。研究表明，长链非编码RNA（lncRNA）与恶性肿瘤的发生、发展密切相关。其中，称为同源框转录反义RNA（HOTAIR）的LncRNA在多种恶性肿瘤（包括PDAC）中的癌症进展中起关键作用。由于HOTAIR在调节下游microRNA（miRNAs）中的作用，许多研究将其与恶性肿瘤治疗的不良预后相关联。然而，其对PDAC的CSC样性质的潜在作用机制仍不清楚。我们用无血清培养基（SFM）富集PDAC的CSC，并分析富集后HOTAIR和miR-34 a的表达水平。此外，我们评估了HOTAIR和miR-34 a对CSC样特性、PDAC的侵袭和迁移的调节作用。最后，我们阐明了HOTAIR在胰腺肿瘤异种移植中的作用。在PDAC的PDAC富集后，在CSC中HOTAIR上调。相反，miR-34 a下调，似乎是HOTAIR的直接靶点。此外，敲低HOTAIR或过表达miR-34 a显著抑制PDAC细胞的CSC样特性、侵袭和迁移。此外，HOTAIR通过miR-34 a激活JAK 2/STAT 3通路，从而促进PDAC细胞的CSC样特性、侵袭和迁移。体内实验表明，敲低HOTAIR可以抑制CFPAC-1细胞的致瘤性。这是HOTAIR通过miR-34 a抑制介导的JAK 2/STAT 3通路激活的首次报道。这种激活促进了CSC样性质、PDAC的侵袭和迁移。
Pancreatic Ductal Adenocarcinoma (PDAC) stem cells (CSCs) play a vital role in the occurrence, development and recurrence of PDAC. Previous studies have shown that long non-coding RNAs (lncRNA) are closely associated with occurrence and development of malignant tumors. Among them, a LncRNA called homeobox transcription antisense RNA (HOTAIR) plays a key role in cancer progression in a variety of malignant tumors, including PDAC. Numerous studies have associated HOTAIR with poor prognosis of malignant tumor treatment, owing to its role in regulating downstream microRNAs (miRNAs). However, its underlying mechanism of action on CSCs-like properties of PDAC remain unclear. We enriched CSCs of PDAC with a serum-free medium (SFM), and analyzed the expression levels of HOTAIR and miR-34a after enrichment. In addition, we evaluated the regulatory effects of HOTAIR and miR-34a on CSCs-like properties, invasion and migration of PDAC. Finally, we elucidated the role of HOTAIR in pancreatic tumor xenotransplantation. HOTAIR was upregulated in CSCs following PDAC enrichment of PDAC. Conversely, miR-34a was downregulated and appeared to be a direct target of HOTAIR. Moreover, knocking down HOTAIR or overexpressing miR-34a significantly inhibited CSCs-like properties, invasion and migration of PDAC cells. Furthermore, HOTAIR activated the JAK2/STAT3 pathway through miR-34a, thereby promoting CSCs-like properties, invasion and migration of PDAC cells. In vivo experiments indicated that knocking down HOTAIR could inhibit the tumorigenicity of CFPAC-1 cells. This is the first report of HOTAIR-mediated activation of the JAK2/STAT3 pathway via miR-34a inhibition. This activation promotes CSCs-like properties, invasion and migration of PDAC.