2. Academic Validation
  3. PARD6A promotes lung adenocarcinoma cell proliferation and invasion through Serpina3

PARD6A promotes lung adenocarcinoma cell proliferation and invasion through Serpina3

  • Cancer Gene Ther. 2024 Sep 19. doi: 10.1038/s41417-024-00829-w.
Lanlin Hu # 1 2 3,  Mingxin Liu # 4,  Bo Tang # 3,  Xurui Li 5 6,  Huasheng Xu 7,  Huani Wang 1 2 3,  Dandan Wang 3 8,  Sijia Liu 9,  Chuan Xu 10 11 12 13
Affiliations

Affiliations

  • 1 Yu-Yue Pathology Scientific Research Center, Chongqing, 400039, China.
  • 2 Jinfeng Laboratory, Chongqing, 401329, China.
  • 3 Department of Oncology & Cancer Institute, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China.
  • 4 Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu, 610042, China.
  • 5 Cancer Center, Medical Research Institute, Southwest University, Chongqing, 400716, China.
  • 6 Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China.
  • 7 Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine & Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration & Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Guangxi Medical University, Nanning, 530021, China.
  • 8 Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
  • 9 Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine & Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration & Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Guangxi Medical University, Nanning, 530021, China. heming_liu@163.com.
  • 10 Yu-Yue Pathology Scientific Research Center, Chongqing, 400039, China. xuchuan100@uestc.edu.cn.
  • 11 Jinfeng Laboratory, Chongqing, 401329, China. xuchuan100@uestc.edu.cn.
  • 12 Department of Oncology & Cancer Institute, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China. xuchuan100@uestc.edu.cn.
  • 13 Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China. xuchuan100@uestc.edu.cn.
  • # Contributed equally.
PMID: 39300216 DOI: 10.1038/s41417-024-00829-w
Abstract

Par6α encoded by PARD6A is a member of the PAR6 family and is reported to promote Cancer initiation and progression. PARD6A is frequently upregulated in different types of cancers, but its regulatory role in lung Cancer progression is yet to be established. In this study, we analyzed the PARD6A expression in biopsies from lung adenocarcinoma (LUAD) patients, and the survival probability using LUAD tissue microarray (TMA) and online datasets from TCGA and GEO. We conducted in vitro and in vivo assays to assess the role of PARD6A in regulating lung Cancer progression, including proliferation, wound healing, transwell, RNA-seq, and subcutaneous tumor mice models. Our findings revealed that PARD6A is highly expressed in Cancer tissues from LUAD patients and is associated with poor prognosis in LUAD patients. In vitro assays showed that PARD6A promoted cell proliferation, migration, and invasion. The transcriptome Sequencing identified Serpina3 as one of the key downstream molecules of PARD6A. Ectopic expression of Serpina3 rescued impaired proliferation, migration, and invasion in PARD6A-knocking down H1299 cells, whereas silencing Serpina3 impeded enhanced proliferation, migration, and invasion in PARD6A-overexpressing H1975 cells. Our findings suggest that PARD6A promotes lung Cancer progression by inducing Serpina3, which may be a promising therapeutic target.

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