The HOXD9-mediated PAXIP1-AS1 regulates gastric cancer progression through PABPC1/PAK1 modulation

被引：13

作者：

Li, Jiaying ^{[1
]}

Pei, Miaomiao ^{[1
]}

Xiao, Wushuang ^{[1
]}

Liu, Xuehua ^{[1
,2
]}

Hong, Linjie ^{[1
]}

Yu, Zhen ^{[1
]}

Peng, Ying ^{[1
]}

Zhang, Jieming ^{[1
]}

Yang, Ping ^{[1
]}

Lin, Jianjiao ^{[3
]}

Wu, Xiaosheng ^{[1
]}

Lin, Zhizhao ^{[1
]}

Tang, Weimei ^{[1
]}

Zhi, Fachao ^{[1
]}

Li, Guoxin ^{[4
]}

Xiang, Li ^{[3
]}

Li, Aimin ^{[1
]}

Liu, Side ^{[1
]}

Chen, Ye ^{[5
]}

Wang, Jide ^{[1
]}

机构：

[1] Southern Med Univ, Nanfang Hosp, Dept Gastroenterol, Guangdong Prov Key Lab Gastroenterol, Guangzhou 510515, Peoples R China

[2] Southern Med Univ, Shunde Hosp, Dept Gastroenterol, Foshan 528300, Peoples R China

[3] Chinese Univ Hong Kong, Affiliated Hosp 2, Shenzhen & Longgang Dist Peoples Hosp Shenzhen, Sch Med,Dept Gastroenterol, Shenzhen 518172, Peoples R China

[4] Southern Med Univ, Nanfang Hosp, Dept Gen Surg, Guangzhou 510515, Peoples R China

[5] Southern Med Univ, Shenzhen Hosp, Integrat Clin Microecol Ctr, Dept Gastroenterol, Shenzhen 518000, Peoples R China

来源：

CELL DEATH & DISEASE | 2023年 / 14卷 / 05期

基金：

中国国家自然科学基金;

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; MESSENGER-RNA; HEPATOCELLULAR-CARCINOMA; POOR-PROGNOSIS; EXPRESSION; INTERACTS; PROMOTES; PAK1; CYTOSKELETON; METASTASIS;

D O I：

10.1038/s41419-023-05862-5

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Long non-coding RNAs (lncRNAs) have been functionally characterised in various diseases. LncRNA PAX-interacting protein 1-antisense RNA 1 (PAXIP1-AS1) has reportedly been associated with cancer development. However, its role in gastric cancer (GC) remains poorly understood. Here, we showed that PAXIP1-AS1 was transcriptionally repressed by homeobox D9 (HOXD9) and was significantly downregulated in GC tissues and cells. Decreased expression of PAXIP1-AS1 was positively correlated with tumour progression, while PAXIP1-AS1 overexpression inhibited cell growth and metastasis both in vitro and in vivo. PAXIP1-AS1 overexpression significantly attenuated HOXD9-enhanced epithelial-to-mesenchymal transition (EMT), invasion and metastasis in GC cells. Poly(A)-binding protein cytoplasmic 1 (PABPC1), an RNA-binding protein, was found to enhance the stability of PAK1 mRNA, leading to EMT progress and GC metastasis. PAXIP1-AS1 was found to directly bind to and destabilise PABPC1, thereby regulating EMT and metastasis of GC cells. In summary, PAXIP1-AS1 suppressed metastasis, and the HOXD9/PAXIP1-AS1/PABPC1/PAK1 signalling axis may be involved in the progression of GC.

引用

页数：14

共 49 条

[1] The relevance of gastric cancer biomarkers in prognosis and pre- and post-chemotherapy in clinical practice [J].