Published online Oct 15, 2026. doi: 10.4251/wjgo.121827
Revised: May 8, 2026
Accepted: May 28, 2026
Published online: October 15, 2026
Processing time: 190 Days and 16.8 Hours
Gastric cancer (GC) remains a major cause of cancer-related death worldwide, and effective molecular targets for advanced disease are still limited. PARVA (alpha-parvin) is a focal adhesion-associated protein involved in cell-matrix interaction and cytoskeletal regulation, but its role in GC remains unclear.
To investigate the expression, biological function, and potential mechanism of PARVA in GC.
PARVA was identified from our previous proteomic screening and further evaluated using public databases. Its expression was validated in GC tissues and cell lines by quantitative real-time PCR, Western blotting, and immunohistochemistry. A tissue microarray containing 107 GC tissues and 22 adjacent normal tissues was used to assess expression and survival association. Gain- and loss-of-function assays were performed to evaluate proliferation, migration, and inva
PARVA was upregulated in GC tissues and cell lines, and high PARVA expression was associated with shorter overall survival. Single-cell analysis showed heterogeneous PARVA expression, with relatively higher levels in fibroblast- and myofibroblast-related populations. Functionally, PARVA knockdown suppressed cell proliferation, migration, and invasion, whereas PARVA overexpression had the opposite effects. In vivo, PARVA silencing inhibited xenograft growth. Mechanistically, RNA sequencing showed significant enrichment of the PI3K/AKT pathway after PARVA knockdown. FBXO15 was identified as a candidate downstream effector, and rescue experiments showed that it partially reversed the effects of PARVA knockdown on malignant phenotypes and pathway activation.
PARVA is upregulated in GC and may promote malignant progression partly through FBXO15-related activation of the PI3K/AKT pathway.
Core Tip: PARVA was identified from previous proteomic screening and validated in gastric cancer. PARVA was up
- Citation: Lu X, Li J, Wang ML, Wang HZ, Li YX. PARVA promotes gastric cancer progression through FBXO15-related PI3K/AKT signaling. World J Gastrointest Oncol 2026; 18(10): 121827
- URL: https://www.wjgnet.com/1948-5204/full/v18/i10/121827.htm
- DOI: https://dx.doi.org/10.4251/wjgo.121827
Gastric cancer (GC) remains one of the most common malignancies of the digestive system worldwide and continues to account for a substantial proportion of cancer-related deaths[1]. In recent years, the diagnosis and treatment of GC and gastroesophageal junction cancer in China have improved steadily, yet the overall survival of patients with advanced disease remains unsatisfactory[2,3]. At the same time, perioperative treatment, immunotherapy, and molecularly targeted therapy have continued to evolve, and biomarkers such as HER2, FGFR2b, CLDN18.2, and PD-L1 have gradually entered clinical decision-making[4,5]. Even so, treatment outcomes are still limited by tumor heterogeneity, acquired resistance, and ongoing disease progression[6]. For this reason, identifying new driver molecules and clarifying their molecular basis remain important tasks in GC research[7].
The malignant progression of GC is not simply a matter of increased proliferation. It is also closely related to altered cell adhesion, cytoskeletal remodeling, and persistent interactions between tumor cells and the surrounding microenvironment[8,9]. Recent studies suggest that heterotypic adhesion between tumor cells and cancer-associated fibroblasts, together with adhesion reprogramming between cells and the extracellular matrix, plays an important part in tumor invasion and metastasis[10]. Against this background, our group previously carried out omics-based screening focused on GC metastasis. In our earlier work, label-free proteomic analysis of primary GC tissues and GC liver metastases showed that the differentially expressed proteins were mainly enriched in cell adhesion- and focal adhesion-related pathways, and further identified the ASF1B/ZDHHC9/PCBP1/SLC7A11 axis as a regulator of liver metastasis in GC[11]. These findings provided a practical basis for further exploring adhesion-related candidates from the same dataset.
PARVA (alpha-parvin), also known as actopaxin or CH-ILKBP, is an important member of the parvin family. As a component of the ILK-PINCH-parvin complex, PARVA participates in cell-matrix adhesion, actin cytoskeleton or
At the signaling level, the focal adhesion system in which PARVA functions may be linked to the PI3K/AKT pathway. The PI3K/AKT/mTOR axis is widely recognized as one of the core pathways involved in GC development and progression, regulating cell proliferation, migration, invasion, metabolic reprogramming, and therapeutic resistance[4]. In parallel, increasing attention has been paid to the F-box protein family in GC, since different members may exert either tumor-promoting or tumor-suppressive effects depending on the biological context[16]. Among them, FBXO15 has been reported to suppress tumor progression in breast cancer[17], whereas its role in GC remains unclear. Based on these observations, we speculated that PARVA may function as more than a focal adhesion-related structural protein and may participate in signaling networks involved in GC progression.
Based on our previous omics screening results and the background described above, we selected PARVA for further investigation. In the present study, we evaluated the expression pattern and clinical relevance of PARVA in GC tissues and cells, and combined in vitro and in vivo functional assays with mechanistic analyses to determine whether PARVA contributes to GC progression through FBXO15-related mechanisms and the PI3K/AKT signaling pathway. Through this work, we sought to extend our previous findings and provide additional evidence for the role of PARVA in GC.
To identify PARVA as a candidate molecule, the label-free proteomic data from our previous study comparing primary GC tissues and GC liver metastasis (GCLM) tissues were reviewed and reorganized. Differentially expressed proteins between primary and metastatic lesions were identified, and the relative abundance of PARVA was displayed.
Public databases were then used to evaluate the expression characteristics and clinical relevance of PARVA in GC. Sangerbox 3.0 was used for pan-cancer differential expression analysis. GEPIA was used to compare PARVA expression between GC and normal gastric tissues. The human protein atlas was used to examine PARVA immunohistochemical staining and its association with survival. TISCH was used to assess the single-cell expression pattern of PARVA in GC, including the STAD_GSE134520 and STAD_GSE167297 datasets.
A total of 107 formalin-fixed, paraffin-embedded GC tissues and 22 adjacent normal tissues were collected from the First Affiliated Hospital of Anhui Medical University between October 2012 and December 2013 for tissue microarray analysis. None of the patients had received preoperative chemotherapy or radiotherapy. Follow-up ranged from 8 months to 71 months. Tumor stage was determined according to the 8th edition of the American Joint Committee on Cancer staging system. Written informed consent was obtained from all patients, and the study was approved by the Biomedical Ethics Committee of Anhui Medical University (Approval No. 20180323).
Paired fresh GC tissues and adjacent non-tumorous tissues were also collected for quantitative real-time PCR (qRT-PCR) and Western blot analysis. All specimens were pathologically confirmed before use.
GES-1, MGC803, HGC27, AGS, MKN45, and SGC7901 cells were obtained from GeneChem (Shanghai, China). Cells were cultured in RPMI-1640 medium (Corning, NY, United States) supplemented with 10% fetal bovine serum (Clark Bioscience, Richmond, VA, United States), 1% penicillin, and 1% streptomycin (HyClone, Logan, UT, United States) in a humidified incubator with 5% CO2 at 37 °C.
Total RNA was extracted from cells or tissues using TRIzol reagent (Invitrogen, CA, United States). Reverse transcription and qRT-PCR were performed according to standard procedures. Primers were synthesized by General Biosystems (Anhui Province, China), and GAPDH served as the internal control. Relative mRNA expression levels were calculated using the 2-ΔΔCt method. Each experiment was performed in triplicate and repeated at least 3 times independently.
Total protein was extracted from cells or tissues using M-PER protein extraction buffer (Thermo Fisher, United States) supplemented with protease and phosphatase inhibitors (BBI Life Sciences Corporation, Shanghai, China). Equal amounts of protein were separated by SDS-PAGE and transferred to PVDF membranes. After blocking, membranes were incubated overnight at 4 °C with primary antibodies and then with HRP-conjugated secondary antibodies. Protein bands were visualized using an enhanced chemiluminescence system and quantified with ImageJ software. Western blot experiments were repeated at least three times independently.
The primary antibodies used were as follows: GAPDH (cat. 7074T; Cell Signaling Technology, Danvers, MA, United States), AKT (cat. R23411; ZenBio, Chengdu, China), p-AKT (cat. R381555; ZenBio, Chengdu, China), PI3K (cat. R381092; ZenBio, Chengdu, China), p-PI3K (cat. 310164; ZenBio, Chengdu, China), PARVA (cat. no. 11202-1-AP; Proteintech, Wuhan, China), and FBXO15 (cat. no. 13024-1-AP; Proteintech, Wuhan, China).
Paraffin sections were deparaffinized, rehydrated, subjected to antigen retrieval, and incubated with anti-PARVA antibody (Proteintech, Wuhan, China; 1:200), followed by secondary antibody incubation and DAB visualization.
PARVA expression in tissue microarrays was independently evaluated by two pathologists blinded to the clinical data. Staining intensity was scored as 0, 1, 2, or 3, and staining area was scored as 0, 1, 2, 3, or 4. The final score was calculated as the product of the intensity score and area score. A final score ≥ 5 was defined as high expression, whereas a score of
Three shRNAs targeting human PARVA and a lentiviral PARVA overexpression construct were obtained from GeneChem (Shanghai, China). Cells were seeded in 12-well plates and infected with lentiviral particles at a multiplicity of infection of 10 according to the manufacturer’s instructions. After infection, cells were selected with 2 mg/mL puromycin and maintained in 1 mg/mL puromycin for subsequent experiments. Western blotting was used to evaluate the knockdown efficiency of the three shRNAs, and sh1 and sh2 were selected for subsequent functional experiments because they showed stable and efficient knockdown.
AGS and HGC27 cells, which expressed relatively high endogenous PARVA, were used for knockdown experiments, whereas SGC7901 cells, which showed relatively low basal PARVA expression, were used for overexpression experi
Cells were seeded into 6-well plates at approximately 800 cells per well. The medium was replaced every 3 days. After about 7 days, when visible colonies had formed, cells were fixed with 4% paraformaldehyde and stained with 0.1% crystal violet. Colonies were counted and photographed after air drying. Each experiment was repeated at least three times independently.
Cell proliferation was evaluated using an EdU assay kit (C0078S; Beyotime, Shanghai, China). Cells were seeded on coverslips in 12-well plates and incubated overnight. The next day, cells were incubated with 2 × EdU working solution, washed with PBS containing 3% bovine serum albumin, permeabilized with 0.3% Triton X-100, and then incubated with Click reaction solution for 30 minutes. Nuclei were counterstained with Hoechst 33342. Images were captured using a Leica microscope (Wetzlar, Germany), and the percentage of EdU-positive cells was calculated. Each experiment was repeated at least three times independently.
Cells were seeded into 6-well plates and grown to approximately 90% confluence. A straight wound was made using a sterile pipette tip. After washing with PBS, cells were cultured in serum-free medium to reduce the influence of proliferation on wound closure. Images were captured at 0 hours, 24 hours, and 48 hours. Wound width was measured using ImageJ, and the relative migration rate was calculated. Each experiment was repeated at least three times independently.
Cells in the logarithmic growth phase were serum-starved for 24 hours before seeding. For invasion assays, Matrigel (BD Biosciences, Shanghai, China) was diluted to working concentration, applied to the upper chamber of a Transwell insert (Corning, United States), and incubated at 37 °C for 5 hours. Cells suspended in serum-free medium were then added to the upper chamber, while medium containing serum was placed in the lower chamber as a chemoattractant. After incubation, cells on the lower surface were fixed, stained with 0.1% crystal violet, and counted under a Leica microscope. For migration assays, the same procedure was used except that no Matrigel coating was applied. Each experiment was repeated at least three times independently.
To investigate downstream molecular changes associated with PARVA, transcriptome sequencing was performed after stable PARVA overexpression. Total RNA was extracted from PARVA-overexpressing cells and matched control cells and submitted to General Biosystems (Anhui Province, China) for library construction and sequencing. Three biological replicates were included in each group. Differentially expressed genes were identified using the thresholds of q < 0.05 and |log2 fold change| > 1. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was then performed, and heatmaps of representative differentially expressed genes were generated to identify pathways and candidate downstream molecules potentially regulated by PARVA.
To determine whether FBXO15 was involved in the biological effects of PARVA, rescue experiments were carried out. In AGS cells, control, PARVA knockdown, and PARVA knockdown plus FBXO15 overexpression groups were established. In SGC7901 cells, control, PARVA overexpression, and PARVA overexpression plus FBXO15 knockdown groups were established. Changes in PI3K/AKT pathway-related proteins, as well as cell proliferation, migration, and invasion, were then examined.
Male BALB/c nude mice (4-6 weeks old, 18-22 g) were obtained from GemPharmatech (Jiangsu Province, China) and maintained under specific pathogen-free conditions in individually ventilated cages, with a 12 hours light/dark cycle, controlled temperature and humidity, and free access to autoclaved food and water. The animals were allowed to acclimate for 4 weeks before experimentation. The experimental unit was a single mouse. Cells were digested, re
Mice were assigned by simple randomization using a random number table to a control group, a PARVA knockdown group, a FBXO15 knockdown group, and a PARVA/FBXO15 double-knockdown group, with 6 mice in each group. The sample size was based on previous experience with subcutaneous xenograft models and available resources, and no formal a priori sample size calculation was performed. Tumor volume was considered the primary animal outcome, whereas tumor weight, body weight, and immunohistochemical staining of Ki67, p-PI3K, and p-AKT were secondary outcomes. Tumor volume and body weight were measured every 3 days in the same order across groups. Tumor volume was calculated as length × width2/2. No formal blinding was applied during tumor measurement, whereas immunohistochemical evaluation was performed in a blinded manner. No predefined exclusion criteria were set after group allocation, and no animal or data point was excluded from the final analysis. Mice were euthanized when body weight loss exceeded 20% or when tumor diameter exceeded 1.5 cm. Tumors were excised, weighed, photographed, and partially fixed for immunohistochemical analysis.
Statistical analyses were performed using SPSS 27.0 (SPSS Inc., Chicago, IL, United States), GraphPad Prism 9.0, and R version 4.5.0. Data are presented as mean ± SD. Unless otherwise indicated, all in vitro experiments were repeated at least 3 times independently. Differences between two groups were analyzed using Student’s t test, and differences among multiple groups were analyzed using one-way ANOVA. Survival curves were generated using the Kaplan-Meier method and compared with the log-rank test. A P value ≤ 0.05 was considered statistically significant.
To clarify why PARVA was selected for further study and to obtain an initial view of its relevance in GC, we first revisited and redrew the label-free proteomic data from our previous comparison of primary GC tissues and GCLM. PARVA was identified as one of the differentially expressed proteins between primary lesions and liver metastases. Both the volcano plot and the heatmap showed a clear difference between GC and GCLM samples, and abundance analysis further indicated that PARVA expression was lower in GCLM than in primary GC samples (log2FC = -1.70, P = 0.016; Supplementary Figure 1). On the basis of this prior screening result, we then examined PARVA using public databases. Pan-cancer analysis in Sangerbox 3.0 showed that PARVA was aberrantly expressed across multiple tumor types, including GC (Figure 1A). GEPIA showed that PARVA expression was higher in GC tissues than in normal gastric tissues (Figure 1B and C). Immunohistochemical data from THPA also indicated evident PARVA protein expression in GC tissues, and higher PARVA expression was associated with poorer overall survival (Figure 1D and E). Single-cell analysis further showed heterogeneous PARVA expression in GC tissues. In the STAD_GSE134520 dataset, PARVA was mainly distributed in fibroblasts and myofibroblasts, with detectable expression in subsets of malignant, gland mucous, and pit mucous cells (Figure 1F and G). In the STAD_GSE167297 dataset, PARVA was likewise mainly expressed in fibroblasts, while expression was also detected in some endothelial and epithelial cells (Supplementary Figure 2). Taken together, the prior proteomic screening and multi-database analyses consistently suggested that PARVA is closely related to GC progression and therefore warranted further functional and mechanistic investigation.
To further validate the expression pattern of PARVA in GC, we first examined its expression in GC cell lines and clinical samples. The qRT-PCR showed that PARVA mRNA expression was significantly higher in MGC803, AGS, SGC7901, HGC27, and MKN45 cells than in the normal gastric epithelial cell line GES-1. PARVA mRNA expression was also higher in GC tissues than in paired adjacent non-tumorous tissues (Figure 2A and B). Western blotting further showed that PARVA protein expression varied among GC cell lines, with relatively higher levels in AGS and HGC27 cells, while an overall increase was also observed in most GC tissue samples (Figure 2C-F). Immunohistochemical analysis of a tissue microarray containing 107 GC tissues and 22 adjacent normal tissues showed obvious differences in PARVA staining intensity among GC cases (Figure 2G). Kaplan-Meier analysis further showed that patients with high PARVA expression had significantly shorter overall survival than those with low expression (Figure 2H). These findings indicate that PARVA is generally upregulated in GC and that its high expression is associated with poorer overall survival.
Because PARVA protein expression was relatively high in AGS and HGC27 cells, three shRNAs targeting PARVA were first tested in these two cell lines. Western blotting showed effective knockdown, and sh1 and sh2 were selected for subsequent functional experiments (Figure 3A). Functional assays showed that PARVA silencing markedly reduced colony formation and decreased the proportion of EdU-positive cells in both cell lines, indicating impaired proliferative capacity (Figure 3B and C). In addition, wound-healing assays showed that PARVA knockdown significantly slowed wound closure in AGS cells. Transwell assays further confirmed that migration and invasion were both reduced after PARVA knockdown in AGS and HGC27 cells (Figure 3D and E). These results indicate that PARVA silencing simultaneously suppresses GC cell proliferation, migration, and invasion, supporting a tumor-promoting role of PARVA in GC.
To further examine the function of PARVA from a gain-of-function perspective, we selected SGC7901 cells, which showed relatively low basal PARVA expression, and established a PARVA overexpression model. Overexpression efficiency was confirmed by Western blotting (Figure 4A). Colony formation and EdU assays showed that PARVA overexpression significantly enhanced the proliferative capacity of SGC7901 cells (Figure 4B-D). At the same time, Transwell assays showed that PARVA overexpression significantly increased the numbers of migrating and invading cells, and wound-healing assays showed a clear acceleration of wound closure (Figure 4E and F). Together with the knockdown data, these findings further support a pro-tumor role of PARVA in GC.
To explore the mechanism by which PARVA promotes GC progression, we performed transcriptome sequencing after PARVA knockdown and subjected the differentially expressed genes to KEGG enrichment analysis. The altered genes were significantly enriched in the PI3K/AKT signaling pathway and several other tumor-related pathways (Figure 5A). Western blotting further showed that, in AGS and HGC27 cells, PARVA knockdown reduced p-PI3K and p-AKT levels without obvious changes in total PI3K or AKT. In contrast, PARVA overexpression in SGC7901 cells increased p-PI3K and p-AKT expression (Figure 5B), suggesting a close association between PARVA and PI3K/AKT pathway activation. Further analysis showed that FBXO15 expression decreased after PARVA knockdown (Figure 5C). Western blotting confirmed that PARVA silencing reduced FBXO15 protein expression, whereas PARVA overexpression increased FBXO15 expression (Figure 5D). In rescue experiments, FBXO15 overexpression partly reversed the reduction in p-PI3K and p-AKT caused by PARVA knockdown in AGS cells, while FBXO15 knockdown partly weakened the increase in p-PI3K and p-AKT induced by PARVA overexpression in SGC7901 cells (Figure 5E). These findings suggest that PARVA may promote PI3K/AKT pathway activation through an FBXO15-related mechanism and thereby contribute to GC progression.
To further define the role of FBXO15 in PARVA-mediated GC progression, FBXO15 was overexpressed in AGS cells after PARVA knockdown. Restoration of FBXO15 partially rescued the decrease in colony formation and the reduction in EdU-positive cells caused by PARVA silencing (Figure 6A-C). In addition, Transwell and wound-healing assays showed that FBXO15 overexpression partly reversed the impaired migration and invasion observed after PARVA knockdown (Figure 6D and E). These findings further support the idea that FBXO15 is functionally involved in the malignant phenotypes regulated by PARVA in GC cells.
To determine whether the in vitro findings could be reproduced in vivo, we established a subcutaneous xenograft model in nude mice and included a control group, a PARVA knockdown group, a FBXO15 knockdown group, and a PARVA/FBXO15 double-knockdown group. Silencing either PARVA or FBXO15 inhibited xenograft growth, whereas simul
Despite recent progress in perioperative therapy, immunotherapy, and biomarker-guided treatment, durable clinical benefit remains limited for many patients with GC, especially in advanced disease[18]. Tumor heterogeneity and acquired resistance continue to restrict treatment efficacy, which makes the identification of new driver molecules still clinically relevant[19,20].
A key point of the present study is that PARVA was not selected in an arbitrary way. It emerged from our previous proteomic comparison between primary GC and GC liver metastases, in which differentially expressed proteins were mainly enriched in adhesion-related pathways, and the ASF1B/ZDHHC9/PCBP1/SLC7A11 axis was subsequently identified as a regulator of liver metastasis[11]. On that basis, we further examined other candidates from the same screening framework and focused on PARVA. In our earlier proteomic dataset, PARVA differed between primary and metastatic lesions, whereas in public databases and in our own tissue samples it was generally upregulated in tumor tissues compared with normal tissues. Rather than being truly contradictory, these findings more likely suggest that PARVA expression may vary across different stages or biological contexts of GC progression.
PARVA belongs to the parvin family and is an important component of the ILK-PINCH-parvin complex, which participates in cell-matrix adhesion, actin cytoskeleton remodeling, and integrin-related signaling[12,13]. Previous work has shown that the role of PARVA is not uniform across tumor types. In breast cancer, PARVA promotes tumor progression and metastasis, whereas in prostate cancer reduced PARVA expression has been linked to enhanced metastatic behavior[14,15]. In our GC model, PARVA was generally increased in tumor tissues and cell lines, and higher expression was associated with shorter overall survival. Functional experiments consistently showed that PARVA knockdown suppressed proliferation, migration, and invasion, whereas PARVA overexpression produced the opposite effects. These data support a tumor-promoting role of PARVA in GC. At the same time, our single-cell analysis showed relatively higher PARVA expression in fibroblast- and myofibroblast-related populations, suggesting that its function may extend beyond tumor-cell intrinsic behavior and may also involve stromal remodeling within the tumor microenvironment.
Our mechanistic data link PARVA to PI3K/AKT signaling. This is biologically plausible, because the PI3K/AKT/mTOR axis is a major oncogenic pathway in GC and regulates proliferation, survival, migration, invasion, metabolic reprogramming, and treatment resistance[21]. In the present study, RNA-seq after PARVA knockdown showed en
Another finding of interest is the involvement of FBXO15. F-box proteins act as substrate-recognition components of SCF-type E3 ubiquitin ligase complexes, and their biological roles vary considerably across tumor types[16]. FBXO15 has been reported to suppress breast cancer progression and to regulate ABCB1/p-glycoprotein through the ubiquitin-proteasome system[17,22]. In contrast, our data showed that FBXO15 decreased after PARVA knockdown and increased after PARVA overexpression in GC cells. More importantly, FBXO15 restoration partially rescued the suppression of PI3K/AKT signaling and malignant phenotypes caused by PARVA silencing. These findings indicate that FBXO15 is functionally involved in PARVA-driven GC progression. At present, however, it is more appropriate to regard FBXO15 as a candidate downstream effector or signaling node associated with PARVA, rather than as a definitively proven direct target.
Several limitations should be acknowledged. The clinical cohort was relatively small and derived from a single center, and the independent prognostic value of PARVA has not yet been validated by multivariable Cox analysis. The mechanistic data support a functional link between PARVA and the FBXO15/PI3K-AKT axis, but they do not yet define how PARVA regulates FBXO15 at the molecular level. In addition, although single-cell data suggest possible stromal involvement, our functional work was performed mainly in tumor cells. The in vivo experiments were based on a subcutaneous xenograft model and therefore provide limited information on orthotopic growth, metastasis, or tumor-stroma interaction. Finally, downstream mediators beyond PI3K/AKT were not explored in depth, and no pharmacologic inhibition experiments or patient-derived models were included[21].
Overall, our data support PARVA as a molecule associated with malignant progression and poorer overall survival in GC. PARVA may promote GC cell proliferation, migration, invasion, and tumor growth, at least in part, through FBXO15-related activation of the PI3K/AKT pathway. Together with our previous proteomic screening and the current single-cell analyses, these findings suggest that PARVA may act not only within tumor cells but also in adhesion remodeling and tumor-stroma interaction in GC tissues. Further work is still needed to clarify how PARVA regulates FBXO15 and to assess its translational value in models that are closer to clinical practice.
In conclusion, PARVA is upregulated in GC and is associated with poorer overall survival. Functional experiments showed that PARVA promotes GC cell proliferation, migration, invasion, and tumor growth in vivo. Mechanistically, PARVA may exert these effects, at least in part, through FBXO15-related activation of the PI3K/AKT signaling pathway. These findings suggest that PARVA may serve as a candidate biomarker and a potential therapeutic target in GC.
We thank the Center for Scientific Research, The First Affiliated Hospital of Anhui Medical University, for technical support and assistance with the experiments.
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