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YWHAG promotes the progression of lung adenocarcinoma through the JAK2/STAT3 pathway

Cancer Cell International volume 25, Article number: 112 (2025) Cite this article

Abstract

YWHAG, also known as 14-3-3-γ, is one of the 14-3-3 isoforms. It can recognize phosphothreonine/phosphoserine residues and plays a critical role in regulating cellular metabolism, signal transduction, the cell cycle, and apoptosis. This study aims to elucidate the specific roles of YWHAG in Lung adenocarcinoma (LUAD). The mRNA expression of YWHAG was upregulated in LUAD and could serve as a potential predictive biomarker for prognosis and therapeutic efficacy, particularly in response to cisplatin, paclitaxel, docetaxel, and erlotinib. Additionally, the YWHAG protein was expressed at higher levels in LUAD tissues with poor differentiation and lymph node metastasis, and it was identified as an independent prognostic factor. Functional assays revealed that silencing YWHAG inhibited the proliferation and migration of lung cancer cells, while promoting apoptosis. Gene Set Enrichment Analysis (GSEA) identified that YWHAG was involved in several key pathways, including mTOR signaling, unfolded protein response, MYC targets and JAK/STAT3 signaling. Western blot analysis revealed that knockdown of YWHAG reduced the expression of p-JAK2 and p-STAT3. In conclusion, our findings suggest that YWHAG could serve as an attractive prognostic biomarker and a potential marker for drug response. Moreover, our study highlights that YWHAG exerts its oncogenic function through the JAK2/STAT3 signaling pathway, offering new insights into potential therapeutic strategies for LUAD.

Introduction

The new incidence and mortality of lung cancer worldwide rank first among malignant tumors [1]. Among them, lung adenocarcinoma (LUAD) accounts for more than 40% of lung cancer and has a tendency to increase year by year [2]. The main treatment options for LUAD include surgery, chemotherapy, radiotherapy, targeted molecular therapy, and immunotherapy. However, many LUAD patients are diagnosed at advanced stages, with an overall five-year survival rate of only 12–16% [3,4,5]. Therefore, exploring the mechanisms that regulate tumor growth and treatment response is becoming more crucial.

Janus Kinase 2 (JAK2) is a member of the non-receptor tyrosine kinase family. It can mediate the activation of signaling molecules after the binding of cytokines and receptors [6]. STAT3 consists of 770 amino acids and can be phosphorylated by JAK [7, 8]. When STAT3 is activated, it enters the nucleus and binds to promoter DNA sequences, leading to transcription of downstream target genes that regulate cell apoptosis, proliferation, and differentiation [9, 10]. Numerous studies have shown that the JAK2/STAT3 signaling pathway is abnormally and highly activated in many types of cancer [11]. The activation of JAK2/STAT3 pathway is closely related to epithelial-mesenchymal transition (EMT) [12]. In addition, in lung cancer, JAK2/STAT3 pathway can enhance the proliferation of cancer cell by downregulating p53 and p21 [13]. It has been shown that activation of REG3A could enhance the JAK2/STAT3 pathway, forming a positive feedback loop between REG3A and JAK2/STAT3. This, in turn, intensifies the cancer-promoting effects of the IL-6/JAK2/STAT3 pathway, ultimately leading to excessive proliferation and tumor formation of pancreatic cancer cells [14].

Tyrosine 3-monooxygenase/tryptophan5-monooxygenase gamma (YWHAG), also known as 14-3-3γ, is one of the 14-3-3 isoforms [15]. The function and expression of 14-3-3 isoforms vary in cancer cells. They can recognize phosphothreonine/phosphoserine residues and play a critical role in regulating cellular metabolism, signal transduction, cell cycle, and apoptosis [16, 17]. It is mainly located in the cytoplasm and is considered a key factor affecting neural development. In recent years, multiple studies have highlighted that YWHAG is pivotal in various malignancies. YWHAG was overexpressed in various malignancies, including gastric cancer, colorectal cancer and glioblastoma, and held potential as a tumor prognostic marker [16, 18, 19]. In breast cancer, YWHAG could inhibit apoptosis of breast cancer cells and enhance their survival. Clinical relevance analyses indicated that YWHAG is also involved in distant metastasis of breast cancer [20, 21]. Besides, it has been shown that YWHAG could promote cell proliferation, migration, and invasion of colorectal cancer by regulating the Wnt/β-catenin pathway [16]. Although increasing evidence suggests that YWHAG plays an important role in various cancers, its role and specific mechanism in the progression of lung adenocarcinoma are still unknown.

In this research, we aimed to elucidate the roles of YWHAG in LUAD and its potential molecular mechanisms. Interestingly, we found that YWHAG was an independent prognostic factor for LUAD. Besides, it could predict the efficacy of various commonly used chemotherapy drugs. We also found that knockdown of YWHAG could inhibit the proliferation and migration of lung cancer cells and promote apoptosis in lung cancer cells through the JAK2/STAT3 signaling pathway.

Materials and methods

Data collection and analysis

The expression data and Kaplan-Meier (K-M) survival curve of YWHAG in various cancers were obtained from https://ualcan.path.uab.edu/ and https://xenabrowser.net/, respectively. GEO datasets (GSE31210, GSE41271 and GSE50081) were downloaded from the National Center for Biotechnology Information (NCBI) GEO repository (http://www.ncbi.nlm.nih.gov/geo). Chemotherapy drug responses predictions for each sample was evaluated using the oncoPredict R package. GSEA enrichment analysis was performed using the R GSVA package.

Immunohistochemistry (IHC) and scores

We collected 133 lung adenocarcinoma specimens and 50 non-cancerous lung tissues from the Second Xiangya Hospital of Central South University. The YWHAG protein was analyzed at a dilution of 1:800 (Rabbit pAb #12381-1-AP, proteintech) following the previously protocols [22, 23]. The IHC score was conducted by two pathologists who were blinded to the clinical information. The final score was defined as the staining intensity score × staining percentage score. Staining intensity score was 0 (negative), 1 (weak), 2 (moderate) and 3 (strong) and staining percentage score was 0 (0%), 1 (1-25%), 2 (26-50%), 3 (51-75%) and 4 (76-100%). Then we defined ≤ 6 as low expression and ≥ 8 as high expression.

Cell culture and transfection

The lung cancer cell lines was obtained from the American Type Culture Collection (ATCC) and maintained in RPMI-1640 medium supplemented with 10% fetal bovine serum (Pricella Biotechnology, China) supplemented with 10% fetal bovine serum (FBS) (Pricella Biotechnology, China). YWHAG silencing sequences (siYWHAG#1 and siYWHAG#2) were synthesized by Genepharma (China). The siRNA sequences were as follows: siYWHAG#1: CGATTAGGCCTGGCTCTTA; siYWHAG#2: GACCUGUCCUGUCUUUGAUTT. Cell transfection was performed following the manufacturer’s instructions. Cell transfections were performed according to the manufacturer’s protocol.

qRT-PCR analysis

Total RNA from lung cancer cells was extracted using TRIzol (Takara, Japan). Reverse transcription was performed using The HiScript® II Q RT SuperMix for qPCR (+ gDNA wiper) (Vazyme, China), followed by qPCR using the ChamQ Universal SYBR qPCR Master Mix (Vazyme, China). The following primers were used: YWHAG (forward: 5’-AGCCACTGTCGAATGAGGAAC-3’, reverse: 5’-CTGCTCAATGCTACTGATGACC-3’), GAPDH (forward: 5’-GGAGCGAGATCCCTCCAAAAT-3’, reverse: 5’-GGCTGTTGTCATACTTCTCATGG-3’).

Western blot assay

Cells were lysed with RIPA buffer for 30 min, followed by centrifugation to obtain the protein supernatant. Proteins were separated by 10% SDS-PAGE and subsequently transferred to a PVDF membrane. The following primary antibodies were used: YWHAG (1:1000, proteintech), GAPDH (1:5000, zen-bioscience), N-cadherin (1:2000, proteintech), STAT3 (1:1000, zen-bioscience), Bcl-2 (1:1000, zen-bioscience), p-STAT3 (1:1000, zen-bioscience), c-Myc (1:1000, zen-bioscience), MMP9 (1:1000, Abclonal Technology), MMP2 (1:1000, Abclonal Technology), c-PARP (1:1000, Cell Signaling Technology), Bim (1:1000, Cell Signaling Technology), Bcl-xl (1:1000, Cell Signaling Technology), Mcl-1 (1:1000, Cell Signaling Technology), p-JAK2 (1:1000, Cell Signaling Technology), JAK2 (1:1000, Cell Signaling Technology).

CCK8 assay

The proliferative ability of lung cancer cells was assessed using the CCK8 assay. Cells were transfected with siNC or siYWHAG and then planted into 96-well plates for different durations. CCK8 reagent was added into cells and incubate for 3 h. Then the cells were measured for absorbance at 450 nm.

Apoptosis analysis

Cells were transfected with siNC or siYWHAG for 48 h and apoptosis was assessed using the Apoptosis Detection Kit (Beyotime) following the manufacturer’s instructions. Flow cytometry was used to determine the apoptosis rate.

Statistical analysis

All statistical analyses were performed using GraphPad 8.0, SPSS24.0 and R software. The relationship between YWHAG protein levels and the clinicopathological factors of LUAD was analyzed using the chi-square test. The prognostic significance of YWHAG expression was assessed by Kaplan-Meier analysis and Cox hazards model. The Spearman test was employed for all correlation analyses, while comparisons between two groups were made using the Student’s t-test. A p-value of less than 0.05 was deemed significant.

Results

The mRNA expression of YWHAG in various tumor tissues and its prognostic significance

First, we examined the mRNA expression of YWHAG in various tumor tissues in the TCGA database and found that it was highly expressed in several types, including LUAD, Lung Squamous Cell Carcinoma (LUSC), Breast invasive carcinoma (BRCA), Colon adenocarcinoma (COAD), Kidney chromophobe (KICH), Kidney renal papillary cell carcinoma (KIRP), Head and Neck squamous cell carcinoma (HNSC) and Prostate adenocarcinoma (PRAD), ect (Fig. 1; all P < 0.001). Additionally, we examined its prognostic significance and found that LUAD patients with low expression of YWHAG had longer overall survival (P = 0.0002588). To gain a more comprehensive understanding of the prognostic significance of YWHAG in LUAD, we further conducted a survival analysis of YWHAG using GEO dataset. Interestingly, we found that in the GSE31210 and GSE50081 cohort, patients with low expression of YWHAG had longer overall survival and progression free survival. Besides, in the GSE41271 dataset, patients with low expression of YWHAG also seemed to have longer overall survival and progression-free survival, but the statistical difference was weak.

Fig. 1
figure 1

The mRNA expression of YWHAG and its prognostic significance. (A) The mRNA expression of YWHAG in pan-cancer. (B) The prognostic significance of YWHAG in HNSC. (C) The prognostic significance of YWHAG in KIRP. (D) The prognostic significance of YWHAG in LUAD. (E) The prognostic significance of YWHAG in GSE31210 dataset. (F) The prognostic significance of YWHAG in GSE41271 dataset. (G) The prognostic significance of YWHAG in GSE50081 dataset. HNSC, Head and Neck squamous cell carcinoma; KIRP, Kidney renal papillary cell carcinoma; LUAD, Lung adenocarcinoma. *P < 0.05; ***P < 0.001; ****P < 0.0001

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Correlation between YWHAG protein and clinicopathological variables in LUAD patients

To investigate the expression of YWHAG protein in local cohort, we employed IHC to assess its subcellular localization and expression level in LUAD and non-cancerous lung tissue (Non-LT). YWHAG protein was mainly localized in the cytoplasm. We defined a high expression of YWHAG as an IHC score of ≥ 6 and found that the high expression rate was 37.6% (50/133) in LUAD tissues, compared to just 10.0% (5/50) in Non-LT tissues, with a statistically significant difference between the two groups (Fig. 2; P < 0.001). We conducted a further analysis of the association between YWHAG protein and clinicopathological features. The results indicated that the high expression rate of YWHAG was significantly higher in lymph node metastasis and poorly differentiated tissues (Table 1; P = 0.039 and P = 0.042).

Table 1 Association between the expression of YWHAG protein and clinicopathological features of LUAD (n = 133)
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Fig. 2
figure 2

The protein expression of YWHAG and its clinical significance. (A) Representative IHC images of YWHAG protein in LUAD and Non-LT tissues. (B) High expression rate of YWHAG protein in LUAD and Non-LT tissues. (C) The prognostic significance of YWHAG protein in LUAD patients. (D) The prognostic significance of pathological grade in LUAD patients. (E) The prognostic significance of clinical stage in LUAD patients. (F) The prognostic significance of LNM status in LUAD patients. IHC, Immunohistochemistry; LUAD, Lung adenocarcinoma; Non-LT, Non-cancerous lung tissue; LNM, lymph node metastasis. ***P < 0.001

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Effects of YWHAG protein expression on the prognosis of LUAD patients

Kaplan-Meier survival analysis was employed to evaluate the survival status of LUAD patients with various clinicopathological features. For LUAD patients, the overall survival of those with high YWHAG protein expression was significantly shorter than that of patients with low expression (P = 0.018; Fig. 2). Moreover, patients with poor differentiation (P = 0.045), clinical stage III (P < 0.001) and lymph node metastasis (P = 0.016) had a shorter survival time. In addition, we also investigated whether YWHAG protein could be served as an independent prognostic factor for LUAD patients. The results showed that high expression of YWHAG (Table 2; P = 0.040) and clinical stage III (P = 0.007) were independent poor prognostic factors for LUAD patients.

Table 2 Univariate and multivariate analysis for OS in LUAD patients
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YWHAG predicted treatment efficacy of chemotherapy and targeted therapy

Chemotherapy and targeted therapy are important treatment options for lung adenocarcinoma patients, so it is crucial to identify molecular targets that can predict their efficacy. In this study, we used the GDSC database to examine whether YWHAG could serve as a predictive indicator of treatment efficacy. A shown in Fig. 3, we observed that the IC50 values of cisplatin, docetaxel, paclitaxel and erlotinib were lower in patients with high YWHAG expression, indicating that these patients are more sensitive to both cisplatin, paclitaxel, docetaxel and erlotinib.

Fig. 3
figure 3

YWHAG predicted treatment efficacy. (A-D) The estimated IC50 of Cisplatin, Docetaxel, Paclitaxel and Erlotinib between two groups in GSE31210 cohort. (E-H) The estimated IC50 of Cisplatin, Docetaxel, Paclitaxel and Erlotinib between two groups in GSE41271 cohort. (I-L) The estimated IC50 of Cisplatin, Docetaxel, Paclitaxel and Erlotinib between two groups in GSE50081 cohort

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The biological functions of YWHAG in lung cancer cells

To elucidate the biological functions of YWHAG, we conducted a series of cell experiments. First, we examined the protein expression of YWHAG in different lung adenocarcinoma cell lines using western blot analysis and found that YWHAG was highly expressed in H1975 and H358, thereby we selected H1975 and H358 for further experiments (Fig. 4). qPCR and Western blot confirmed the successful knockdown of YWHAG. The CCK8 assays showed that YWHAG knockdown significantly inhibited the proliferation ability of H1975 and H358 cells. Besides, flow cytometry experiments showed that YWHAG knockdown significantly increased the apoptosis ability of lung cancer cells. Additionally, transwell assays confirmed that YWHAG knockdown inhibited the migratory capabilities of H1975 and H358. Furthermore, we measured the expression of apoptosis-related proteins and found that after knockdown of YWHAG, c-PARP and Bim increased while Mcl-1, Bcl-xl and Bcl-2 decreased. We also examined the expression levels of migration and invasion-related proteins and found that N-cadherin, MMP9 and MMP2 were decreased following YWHAG knockdown.

Fig. 4
figure 4

The biological functions of YWHAG in lung cancer cells. (A) Protein expression of YWHAG in bronchial epithelial cell and different lung cancer cell lines. (B) mRNA expression of YWHAG in H1975 and H358 with YWHAG knockdown. (C) Protein expression of YWHAG in H1975 and H358 with YWHAG knockdown. (D) CCK8 analysis of H1975 and H358 with YWHAG knockdown. (E) Apoptosis level of H358 cells with YWHAG knockdown. (F) Apoptosis level of H1975 cells with YWHAG knockdown. (G) Transwell assays of H1975 and H358 with YWHAG knockdown. (H) Western blot analysis of protein expression levels related to apoptosis and migration invasion. **P < 0.01; ***P < 0.001; ****P < 0.0001

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YWHAG exerted its functions by regulating the JAK2/STAT3 signaling pathway

To gain deeper insights into the potential mechanisms of action of YWHAG, we conducted GSEA enrichment analysis in database GSE31210, GSE41271 and GSE50081. The top 10 pathways were displayed in Fig. 5A-C. Besides, The results showed that there were 24 common pathways across the three datasets, including mTOR signaling, unfolded protein response, myc targets and JAK/STAT3 signaling. The JAK/STAT3 signaling pathway caught our attention, as it was involved in various biological behaviors of tumors. Therefore, we examined the expression levels of key proteins in this signaling pathway after YWHAG knockdown. We found that the expression levels of p-JAK2 and p-STAT3 were significantly reduced following YWHAG knockdown, while JAK2, STAT3 and c-Myc did not show significant changes. All these results indicated that YWHAG can regulate the JAK2/STAT3 signaling pathway.

Fig. 5
figure 5

YWHAG regulated the JAK2/STAT3 signaling pathway. (A) GSEA enrichment analysis in the GSE31210 dataset. (B) GSEA enrichment analysis in the GSE41271 dataset. (C) GSEA enrichment analysis in the GSE50081 dataset. (D) Venn diagram for GSEA enrichment analysis of three databases. (E) JAK/STAT3 signaling was enriched in GSE31210 dataset. (F) JAK/STAT3 signaling was enriched in GSE41271 dataset. (G) JAK/STAT3 signaling was enriched in GSE50081. (H) Western blot analysis of protein expression levels related to JAK2/STAT3 signaling pathway

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Discussion

Lung cancer, with the highest incidence and mortality rates, remains a significant threat to human health. Despite the emergence of various combination treatment options, including surgery, targeted therapy, radiochemotherapy and immunotherapy, the overall prognosis for patients remains unsatisfactory [24]. Among the different subtypes of lung cancer, LUAD represents the majority of lung cancer. Thus, understanding the specific molecular mechanisms underlying LUAD is crucial for identifying new therapeutic targets and improving patient outcomes.

YWHAG is a member of the YWHA protein family and was first identified as a factor influencing neurodevelopment [25]. It is a genetically highly conserved protein family that is involved in various intracellular signaling processes. In recent years, abnormal expression of YWHAG has been reported in various malignant tumors, closely related to the aggressive biological behavior of the tumors. However, so far, the clinical significance and mechanisms of action of YWHAG in LUAD remain unclear.

In this study, we first examined the mRNA expression of YWHAG in various tumor tissues and found that mRNA expression of YWHAG was significantly higher in multiple tumor tissues, including LUAD and LUSC, compared to their corresponding normal controls. In addition, we also explored the prognostic significance of YWHAG mRNA. The results indicated that patients with high expression of YWHAG had shorter survival times in HNSC, KICH, KIRP, and LUAD. To further explore the prognostic significance of YWHAG in lung adenocarcinoma tissues, we downloaded relevant data from the GEO database and found that LUAD patients with low mRNA expression of YWHAG had longer overall survival. In addition, we also explored the clinical significance of YWHAG protein in LUAD. We collected LUAD tissues from local cohort and performed immunohistochemical staining. The results indicated that the protein expression of YWHAG was higher in LUAD tissues and was related to pathological grade and lymph node metastasis, which suggests that YWHAG may be involved in the malignant progression of LUAD. Besides, we found that LUAD patients with high levels of YWHAG protein expression had shorter survival times, which was consistent with previous research findings [26]. Chemotherapy and targeted therapy are crucial treatment methods for LUAD patients, but resistance often develops in the end [27, 28]. Therefore, identifying molecular targets to predict treatment efficacy is of significant importance. We utilized the GDSC database to explore the potential therapeutic efficacy for LUAD patients, which was a common database for predicting drug efficacy [29]. Our findings indicated that patients with high YWHAG expression exhibited lower IC50 values for cisplatin, paclitaxel, docetaxel, and erlotinib, suggesting that they might respond better to these drugs. This implied that the YWHAG could be used to guide clinical treatment decisions.

The above results suggested that YWHAG has significant clinical importance. To further explore its biological functions, we carried out a series of cellular experiments. First, we detected the expression levels of YWHAG proteins in different lung cancer cell lines and found that YWHAG had the highest expression in H1975 and H358 cells. Then, we established YWHAG knockdown cell lines. The results indicated that knocking down YWHAG suppressed the proliferation of lung cancer cells and promoted their apoptosis. Poly(ADP-ribose) polymerase (PARP) is an enzyme involved in DNA repair and a substrate for the core apoptotic member caspase. Cleaved PARP is one of the important markers of apoptosis [30, 31]. Research has shown that the ratio of pro-apoptotic to anti-apoptotic proteins determines the occurrence of apoptosis to some extent. Therefore, we examined the expression of apoptosis-related proteins. The results indicated that after knocking down YWHAG, the pro-apoptotic protein Bim significantly increased, while the expression of anti-apoptotic proteins Mcl-1, Bcl-xL, and Bcl-2 significantly decreased. Additionally, the expression of the early apoptosis marker cleaved-PARP also significantly increased, further demonstrating at the protein level that knocking down YWHAG induces apoptosis in lung cancer cells. In addition, this study also validated the effect of YWHAG on the migratory ability of lung cancer cells through Transwell experiments. We found that knockdown of YWHAG exhibited anti-migratory effects, as evidenced by the reduced expression of migration and invasion-related proteins, including N-cadherin, MMP9 and MMP2.

The above results indicated that YWHAG might play an important role in the occurrence and development of lung cancer and could serve as a new therapeutic target. Therefore, elucidating the molecular mechanisms of YWHAG will help guide the development of targeted treatment strategies. Through GSEA enrichment analysis, we found that YWHAG could influence the mTOR signaling pathway, unfolded protein response, Myc targets, and JAK/STAT3 signaling pathways, among others. The JAK/STAT signaling pathway plays a crucial role in cell development, proliferation, differentiation, and survival. It is involved in the signaling processes of cytokines related to immune responses, inflammation, and cell activation and survival [32]. STAT3 is one of the members of the STAT family. It can be phosphorylated by receptor-associated Janus kinases in response to cytokines and growth factors. Once activated, STAT3 dimerizes into either homodimers or heterodimers and subsequently enters the nucleus, where it binds to specific sites on the promoter sequences of target genes to regulate their transcriptional expression [33, 34]. JAK2 is one of the important members of the Janus kinase family. Multiple studies have demonstrated that inhibiting the JAK2/STAT3 pathway could suppress tumor progression [35,36,37,38]. In this study, we initially explored the effect of YWHAG on the JAK2/STAT3 pathway in H9175 and H358. We found that knockdown of YWHAG significantly inhibited the expression of p-JAK2 and p-STAT3. However, the specific molecular mechanisms by which YWHAG regulates the JAK2/STAT3 pathway warrant further investigation in future experiments.

In conclusion, our findings suggest that YWHAG could serve as an attractive prognostic biomarker and as a potential marker for drug response. Moreover, our study indicates that YWHAG exerts its oncogenic function through the JAK2/STAT3 signaling pathway. This research provides new insights into potential therapeutic strategies for LUAD.

Data availability

Data is provided within the manuscript.

Abbreviations

LUAD:

Lung adenocarcinoma

YWHAG:

Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, gamma

JAK2:

Janus kinase 2

EMT:

Epithelial-mesenchymal transition

IHC:

Immunohistochemistry

LUSC:

Lung squamous cell carcinoma

BRCA:

Breast invasive carcinoma

COAD:

Colon adenocarcinoma

KICH:

Kidney chromophobe

KIRP:

Kidney renal papillary cell carcinoma

HNSC:

Head and neck squamous cell carcinoma

PRAD:

Prostate adenocarcinoma

Non-LT:

Non-cancerous lung tissue

PARP:

Poly(ADP-ribose) polymerase

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Funding

This work was supported by the National Natural Science Foundation of China (No: 82272722, 81773218, 82102805), the Natural Science Foundation of Hunan Province (No: 2025JJ60603, 2021JJ40890), Hunan Provincial Health High-Level Talent Scientific Research Project (No: R2023091); National Key Clinical Specialty Scientific Research Project (No: Z2023076).

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Authors and Affiliations

  1. Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China

    Hongmei Zheng, Yaoxiang Tang, Hongjing Zang, Jiadi Luo, Hanqiong Zhou, Ying Zou & Songqing Fan

  2. Hunan Clinical Medical Research Center for Cancer Pathogenic Genes Testing and Diagnosis, Changsha, Hunan, 410011, China

    Hongmei Zheng, Yaoxiang Tang, Hongjing Zang, Jiadi Luo, Hanqiong Zhou, Ying Zou & Songqing Fan

  3. Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China

    Jinwu Peng

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  1. Hongmei Zheng
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Contributions

H.Z. and S.F. wrote the main manuscript text, H.Z., Y.T., H.Z., J.L., H.Z., Y.Z.and J.P. prepared Figs. 1, 2, 3, 4 and 5. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Jinwu Peng or Songqing Fan.

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Ethics approval and consent to participate

This study was approved by The Ethics Review Committee of The Second Xiangya Hospital (No.YF2021048). All procedures involving human participants were conducted in compliance with ethical standards.

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The authors declare no competing interests.

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Zheng, H., Tang, Y., Zang, H. et al. YWHAG promotes the progression of lung adenocarcinoma through the JAK2/STAT3 pathway. Cancer Cell Int 25, 112 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12935-025-03730-0

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Keywords

Cancer Cell International

ISSN: 1475-2867

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