PPP2R1A silencing suppresses LUAD progression by sensitizing cells to nelfinavir-induced apoptosis and pyroptosis

Yating Liu; Lianlian Ouyang; Shiyao Jiang; Lu Liang; Yuanbing Chen; Chao Mao; Yiqun Jiang; Li Cong

doi:10.1186/s12935-024-03321-5

PPP2R1A silencing suppresses LUAD progression by sensitizing cells to nelfinavir-induced apoptosis and pyroptosis

Cancer Cell Int. 2024 Apr 23;24(1):145. doi: 10.1186/s12935-024-03321-5.

Authors

Yating Liu^#¹, Lianlian Ouyang^#^{1

2

3}, Shiyao Jiang^{4

5}, Lu Liang^{4

5}, Yuanbing Chen⁶, Chao Mao⁷, Yiqun Jiang^{8

9}, Li Cong^{10

11}

Affiliations

¹ Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
² Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, 410011, China.
³ Research Unit of Key Technologies of Diagnosis and Treatment for Immune-Related Skin Diseases, Chinese Academy of Medical Sciences, Changsha, 410011, China.
⁴ The Key Laboratory of Model Animal and Stem Cell Biology in Hunan Province, Hunan Normal University, Changsha, 410013, Hunan, People's Republic of China.
⁵ School of Medicine, Hunan Normal University, Changsha, 410013, Hunan, People's Republic of China.
⁶ Department of Neurosurgery, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
⁷ Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁸ The Key Laboratory of Model Animal and Stem Cell Biology in Hunan Province, Hunan Normal University, Changsha, 410013, Hunan, People's Republic of China. jiangyiqun@hunnu.edu.cn.
⁹ School of Medicine, Hunan Normal University, Changsha, 410013, Hunan, People's Republic of China. jiangyiqun@hunnu.edu.cn.
¹⁰ The Key Laboratory of Model Animal and Stem Cell Biology in Hunan Province, Hunan Normal University, Changsha, 410013, Hunan, People's Republic of China. congli@hunnu.edu.cn.
¹¹ School of Medicine, Hunan Normal University, Changsha, 410013, Hunan, People's Republic of China. congli@hunnu.edu.cn.

^# Contributed equally.

Abstract

Lung adenocarcinoma is a major public health problem with the low 5-year survival rate (15%) among cancers. Aberrant alterations of meiotic genes, which have gained increased attention recently, might contribute to elevated tumor risks. However, systematic and comprehensive studies based on the relationship between meiotic genes and LUAD recurrence and treatment response are still lacking. In this manuscript, we first confirmed that the meiosis related prognostic model (MRPM) was strongly related to LUAD progression via LASSO-Cox regression analyses. Furthermore, we identified the role of PPP2R1A in LUAD, which showed more contributions to LUAD process compared with other meiotic genes in our prognostic model. Additionally, repression of PPP2R1A enhances cellular susceptibility to nelfinavir-induced apoptosis and pyroptosis. Collectively, our findings indicated that meiosis-related genes might be therapeutic targets in LUAD and provided crucial guidelines for LUAD clinical intervention.

Keywords: Lung adenocarcinoma; Meiotic genes; Nelfinavir; PPP2R1A; Prognostic model.

Abstract

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