RP11-874 J12.4 promotes erlotinib resistance in non-small cell lung cancer via increasing AXL expression

Shaobo Huang; Jinling Zhang; Xiaoliang Wu; Baoxia Liang; Nengzhi Pang; Lili Yang; Zhenfeng Zhang

doi:10.1016/j.lfs.2024.122849

RP11-874 J12.4 promotes erlotinib resistance in non-small cell lung cancer via increasing AXL expression

Life Sci. 2024 Aug 15:351:122849. doi: 10.1016/j.lfs.2024.122849. Epub 2024 Jun 17.

Authors

Shaobo Huang¹, Jinling Zhang², Xiaoliang Wu³, Baoxia Liang⁴, Nengzhi Pang⁵, Lili Yang⁶, Zhenfeng Zhang⁷

Affiliations

¹ Cancer center, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, China.
² Department of Radiology; Translational Medicine Center and Guangdong Provincial Education, Department Key Laboratory of Nano-Immunoregulation Tumor Microenvironment, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China.
³ Department of Oncology, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China.
⁴ The School of Food Science and Biology, Guangdong Polytechnic of Science and Trade, Guangzhou, China.
⁵ Department of Nutrition; Guangdong Provincial Key Laboratory of Food, Nutrition and Health; School of Public Health, Sun Yat-Sen University, Guangzhou, China.
⁶ Department of Nutrition; Guangdong Provincial Key Laboratory of Food, Nutrition and Health; School of Public Health, Sun Yat-Sen University, Guangzhou, China. Electronic address: [email protected].
⁷ Department of Radiology; Translational Medicine Center and Guangdong Provincial Education, Department Key Laboratory of Nano-Immunoregulation Tumor Microenvironment, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. Electronic address: [email protected].

PMID: 38897346
DOI: 10.1016/j.lfs.2024.122849

Abstract

EGFR tyrosine kinase inhibitor (TKI) resistance is a major challenge for EGFR-mutant non-small cell lung cancer (NSCLC) treatment. Our previous work revealed that overexpression of AXL promoted EGFR-TKI resistance through epithelial-mesenchymal transition (EMT) in a subset of NSCLC patients. Compared with erlotinib resistant and sensitive cells, RP11-874 J12.4 was upregulated in erlotinib-resistant NSCLC cells (HCC827-ER3). Interestingly, the expression of RP11-874 J12.4 positively correlated with AXL. Besides, RP11-874 J12.4 promotes NSCLC cell proliferation and metastasis in vitro. Mechanistically, RP11-874 J12.4 promoted AXL expression through sponge with miR-34a-5p, which was reported to inhibit the translation of AXL mRNA. Meanwhile, the expression of RP11-874 J12.4 in lung cancer tumors were higher than the adjacent tissue, and those patients with high expression of RP11-874 J12.4 showed a poor prognosis in clinical. High expression of RP11-874 J12.4 might be a biomarker for NSCLC patients with erlotinib resistance. These findings reveal a novel insight into the mechanism of erlotinib resistance in NSCLC, and it might be a promising target for the diagnosis and treatment of NSCLC.

Keywords: AXL; Erlotinib-resistance; Non-small cell lung cancer; RP11-874 J12.4.

MeSH terms

Animals
Axl Receptor Tyrosine Kinase*
Carcinoma, Non-Small-Cell Lung* / drug therapy
Carcinoma, Non-Small-Cell Lung* / genetics
Carcinoma, Non-Small-Cell Lung* / metabolism
Carcinoma, Non-Small-Cell Lung* / pathology
Cell Line, Tumor
Cell Proliferation / drug effects
Drug Resistance, Neoplasm* / genetics
Epithelial-Mesenchymal Transition / drug effects
Epithelial-Mesenchymal Transition / genetics
Erlotinib Hydrochloride* / pharmacology
Erlotinib Hydrochloride* / therapeutic use
Gene Expression Regulation, Neoplastic / drug effects
Humans
Lung Neoplasms* / drug therapy
Lung Neoplasms* / genetics
Lung Neoplasms* / metabolism
Lung Neoplasms* / pathology
Mice
MicroRNAs / genetics
MicroRNAs / metabolism
Protein Kinase Inhibitors / pharmacology
Protein Kinase Inhibitors / therapeutic use
Proto-Oncogene Proteins* / genetics
Proto-Oncogene Proteins* / metabolism
Receptor Protein-Tyrosine Kinases* / genetics
Receptor Protein-Tyrosine Kinases* / metabolism

Substances

Erlotinib Hydrochloride
Axl Receptor Tyrosine Kinase
Proto-Oncogene Proteins
Receptor Protein-Tyrosine Kinases
AXL protein, human
Protein Kinase Inhibitors
MicroRNAs
MIRN34 microRNA, human