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Updated: Jul 29, 2025

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
The HOXD9-mediated PAXIP1-AS1 regulates gastric cancer progression through PABPC1/PAK1 modulation
Jiaying Li1, Miaomiao Pei1, Wushuang Xiao1
1Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Abstract:
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.
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