MicroRNA (let-7b-5p)-targeted DARS2 regulates lung adenocarcinoma growth by PI3K/AKT signaling pathway

Sep 21, 2026

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Background: Aberrant mitochondrial aspartyl-tRNA synthetase 2 (DARS2) expression has been reported in human cancers, but its role and mechanism in lung adenocarcinoma (LUAD) remain unclear. Methods: DARS2 prognostic relevance was analyzed using TCGA-based GEPIA, and LUAD cell functions were assessed by CCK-8, immunostaining, and transwell invasion; tumorigenicity was tested in nude mice. Results: LUAD tissues show higher DARS2 than normal, correlating with TNM stage and lymph node metastasis, and DARS2 silencing reduces proliferation, migration, and invasion. PI3K/AKT inactivation accompanied altered PCNA, cleaved-caspase 3, and E/N-cadherin. let-7b-5p directly recognizes DARS2. Conclusion: let-7b-5p downregulates DARS2 and modulates LUAD progression via PI3K/AKT signaling.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

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Introduction

Methods

Results

Conclusion

ONCOLOGY RESEARCH 2024 32(3): 517-528 MicroRNA (let-7b-5p)-targeted DARS2 regulates lung adenocarcinoma growth by PI3K/AKT signaling pathway YUANYUAN XU; XIAOKE CHEN* Department of Oncology Surgery, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China Key words: Lung adenocarcinoma, Prognosis, PI3K/AKT pathway, Mitochondrial aspartyl-tRNA synthetase, MicroRNAs Abstract: Background: The aberrant intracellular expression of a mitochondrial aspartyl-tRNA synthetase 2 (DARS2) has been reported in human cancers. Nevertheless, its critical role and detailed mechanism in lung adenocarcinoma (LUAD) remain unexplored. Methods: Initially, The Cancer Genome Atlas (TCGA)-based Gene Expression Proﬁling Interactive Analysis (GEPIA) database ([http://gepia.cancer-pku.cn/](http://gepia.cancer-pku.cn/)) was used to analyze the prognostic relevance of DARS2 expression in LUAD. Further, cell counting kit (CCK)-8, immunostaining, and transwell invasion assays in LUAD cell lines in vitro, as well as DARS2 silence on LUAD by tumorigenicity experiments in vivo in nude mice, were performed. Besides, we analyzed the expression levels of p-PI3K (phosphorylated-Phosphotylinosital3 kinase), PI3K, AKT (Protein Kinase B), p-AKT (phosphorylated-Protein Kinase B), PCNA (proliferating cell nuclear antigen), cleaved-caspase 3, E-cadherin, and N-cadherin proteins using the Western blot analysis. Results: LUAD tissues showed higher DARS2 expression compared to normal tissues. Upregulation of DARS2 could be related to Tumor-Node-Metastasis (TNM) stage, high lymph node metastasis, and inferior prognosis. DARS2 silence decreased the proliferation, migration, and invasion abilities of LUAD cells. In addition, the DARS2 downregulation decreased the PCNA and N-cadherin expression and increased cleaved-caspase 3 and E-cadherin expressions in LUAD cells, coupled with the inactivation of the PI3K/AKT signaling pathway. Moreover, DARS2 silence impaired the tumorigenicity of LUAD in vivo. Interestingly, let-7b-5p could recognize DARS2 through a complementary sequence. Mechanistically, the increased let-7b-5p expression attenuated the promo-oncogenic action of DARS2 during LUAD progression, which were inversely correlated to each other in the LUAD tissues. Conclusion: In summary, let-7b-5p downregulated DARS2 expression, regulating the progression of LUAD cells by the PI3K/AKT signaling pathway. Introduction Lung cancer, a lethal malignancy arising from the respiratory epithelium, has emerged as one of the most lethal cancers, accounting for the enormous mortality of patients. According to 2020 statistics, a total of 228,820 newly estimated cases and 135,720 deaths were reported, accounting for 12.67% and 22.38% of all cancers, respectively [1] . Among various lung cancers, lung adenocarcinoma (LUAD) is the most common type, with an undesirable 5-year survival rate of around 18.0%[2] . The principal reasons could be insidious symptoms of LUAD and prognosis at the advanced stages, resulting in a deprived response to the treatment modalities. More often, the substantial treatment options for LUAD mainly rely on initial surgical resection followed by the *Address correspondence to: Xiaoke Chen, [huut114@sina.com](huut114@sina.com)[ ](huut114@sina.com)[Received: 29 March 2023](Received: 29 March 2023); [Accepted: 09 June 2023](Accepted: 09 June 2023); Published: 06 February 2024 systemic chemotherapeutic regimen [3] . Accordingly, there isan urgent need to identify critical biomarkers for early diagnosis and interpret their underlying mechanisms to reduce the disease burden. To this end, the mitochondrial aspartyl-tRNA synthetase 2 (DARS2) is located in chromosome 1q25.1, containing 18 exons, resulting in the protein of the class-II aminoacyltRNA synthetase family. This mitochondrial enzyme plays a crucial role in the aminoacylation of aspartyl-tRNA explicitly. Oftentimes, mutations in DARS2 result in leu

FAQs

How was the relationship between DARS2 expression and LUAD prognosis evaluated?

DARS2 prognostic relevance in LUAD was analyzed using the TCGA-based GEPIA database.

What effects did DARS2 silencing have on LUAD cells and tumor growth?

DARS2 silencing decreased LUAD cell proliferation, migration, and invasion, and impaired tumorigenicity in vivo in nude mice.

What mechanism links let-7b-5p to DARS2 in LUAD?

let-7b-5p recognizes DARS2 through a complementary sequence, and increased let-7b-5p attenuates the pro-oncogenic action of DARS2, which are inversely correlated in LUAD tissues.

Sep 21, 2026

Uploaded by Patrick