1. Academic Validation
  2. ELAVL4 promotes the tumorigenesis of small cell lung cancer by stabilizing LncRNA LYPLAL1-DT and enhancing profilin 2 activation

ELAVL4 promotes the tumorigenesis of small cell lung cancer by stabilizing LncRNA LYPLAL1-DT and enhancing profilin 2 activation

  • FASEB J. 2023 Oct;37(10):e23170. doi: 10.1096/fj.202300314RR.
Shuxin Li 1 Jianyi Lv 1 Xing Zhang 1 Qiuyu Zhang 1 Zhihui Li 1 Jing Lu 1 Xueyun Huo 1 Meng Guo 1 Xin Liu 1 Ran Gao 2 Jianan Gong 2 Changlong Li 1 Weiying Li 3 Tongmei Zhang 3 Jinghui Wang 3 Zhenwen Chen 1 Xiaoyan Du 1
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Capital Medical University, Beijing Key Laboratory of Cancer Invasion & Metastasis Research, Beijing, P.R. China.
  • 2 Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS); and Comparative Medicine Center, Peking Union Medical College (PUMC), Beijing, China.
  • 3 Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.
Abstract

Small cell lung Cancer (SCLC) is one of the most malignant tumors that has an extremely poor prognosis. RNA-binding protein (RBP) and long noncoding RNA (lncRNA) have been shown to be key regulators during tumorigenesis as well as lung tumor progression. However, the role of RBP ELAVL4 and lncRNA LYPLAL1-DT in SCLC remains unclear. In this study, we verified that lncRNA LYPLAL1-DT acts as an SCLC oncogenic lncRNA and was confirmed in vitro and in vivo. Mechanistically, LYPLAL1-DT negatively regulates the expression of miR-204-5p, leading to the upregulation of PFN2, thus, promoting SCLC cell proliferation, migration, and invasion. ELAVL4 has been shown to enhance the stability of LYPLAL1-DT and PFN2 mRNA. Our study reveals a regulatory pathway, where ELAVL4 stabilizes PFN2 and LYPLAL1-DT with the latter further increasing PFN2 expression by blocking the action of miR-204-5p. Upregulated PFN2 ultimately promotes tumorigenesis and invasion in SCLC. These findings provide novel prognostic indicators as well as promising new therapeutic targets for SCLC.

Keywords

ELAVL4; lncRNA LYPLAL1-DT; profilin 2; small cell lung cancer; tumorigenesis.

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