PDLIM5 inhibits STUB1-mediated degradation of SMAD3 and promotes the migration and invasion of lung cancer cells

Shi, Yueli; Wang, Xinyu; Xu, Zhiyong; He, Ying; Guo, Chengxiang; He, Lingjuan; Huan, Caijuan; Cai, Changhong; Huang, Jiaqi; Zhang, Jie; Li, Yiqing; Zeng, Chunlai; Zhang, Xue; Wang, Linrun; Ke, Yuehai; Cheng, Hongqiang

doi:10.1074/jbc.ra120.014976

Cited by 48 publications

(32 citation statements)

References 49 publications

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“…In NSCLC, TGF-β signaling is frequently enhanced and promotes EMT and tumor metastasis, whereas SMAD3 inhibition diminished TGF-β-induced EMT in cancer cells [ 29 ]. In addition, SMAD3 overexpression was demonstrated to accelerate TGF-β-mediated NSCLC metastasis [ 30 ]. In this work, the oncogenic role of SMAD3 in NSCLC via activating RAB26 expression was uncovered.…”

Section: Discussionmentioning

confidence: 99%

RAB26 contributes to the progression of non-small cell lung cancer after being transcriptionally activated by SMAD3

Ren

Yang

et al. 2022

Bioengineered

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Non-small cell lung cancer (NSCLC) accounts for 85% of all cases of lung cancer, which constitutes the leading cause of cancer mortality. RAB26, a member of Rab GTPase superfamily, has been suggested to play a role in the tumorigenesis of NSCLC. The present work aimed to explore whether and how RAB26 contributed to the progression of NSCLC. NSCLC cell line A549 was transfection with short hairpin RNA (shRNA) or overexpression (Ov) vector to knockdown RAB26 or overexpress SMAD3, respectively. Then the malignant processes of A549 cells including proliferation, migration, invasion and apoptosis were evaluated by CCK-8, colony formation, wound-healing, transwell and TUNEL assays, respectively. Expression of proteins involved in these processes was measured by western blot. A549 xenograft mice model was established to confirm the effect of RAB26 silence on NSCLC progression in vivo. The relationship between RAB26 and SMAD3 was analyzed by bioinformatics and then verified by dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. We found that silence of RAB26 inhibited the proliferation, migration and invasion but promoted apoptosis of A549 cells. In vivo studies revealed that the tumor growth of A549 xenograft was markedly suppressed upon RAB26 silence. Moreover, it was confirmed that SMAD3 bound to the promoter of RAB26 and enhance its expression. Finally, we observed that overexpression of SMAD3 significantly blocked the inhibitory effect of RAB26 silence on NSCLC progression. Collectively, RAB26 may contribute to the progression of NSCLC after being transcriptionally activated by SMAD3.

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Section: Discussionmentioning

confidence: 99%

RAB26 contributes to the progression of non-small cell lung cancer after being transcriptionally activated by SMAD3

Ren

Yang

et al. 2022

Bioengineered

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“…The PDLIM5 gene is a protein that binds to several proteins, such as PKC, PKA, PKD, and AMPK, and is important in signal modulation pathways [ 18 ]. In our study, rs12500426 was associated with higher mortality and incidence, being more frequent in Africans.…”

Section: Discussionmentioning

confidence: 99%

Correlation between Genomic Variants and Worldwide Epidemiology of Prostate Cancer

Vieira

Gellen

Leal

et al. 2022

Genes

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Prostate cancer (PCa) incidence and mortality vary across territories and populations. This can be explained by the genetic factor of this disease. This article aims to correlate the epidemiological data, worldwide incidence, and mortality of PCa with single-nucleotide polymorphisms (SNPs) associated with the susceptibility and severity of this neoplasm in different populations. Eighty-four genetic variants associated with prostate cancer susceptibility were selected from the literature through genome association studies (GWAS). Allele frequencies were obtained from the 1000 Genomes Project, and epidemiological data were obtained from Surveillance, Epidemiology, and End Results (SEER). The PCa incidence, mortality rates, and allele frequencies of variants were evaluated by Pearson’s correlation. Our study demonstrated that 12 SNPs (rs2961144, rs1048169, rs7000448, rs4430796, rs2066827, rs12500426, rs6983267, rs11649743, rs2075110, rs114798100, rs855723, and rs2075109) were correlated with epidemiological data in different ethnic groups. Ten SNPs (rs2961144, rs1048169, rs7000448, rs4430796, rs2066827, rs12500426, rs11649743, rs2075110, rs114798100, and rs2075109) were positively correlated with the mortality rate. Seven SNPs (rs1048169, rs2961144, rs7000448, rs4430796, rs2066827, rs12500426, and rs114798100) were positively correlated with incidence. Positive correlations of incidence and mortality rates were more frequent in the African population. The genetic variants investigated here are likely to predispose to PCa and could play a role in its progression and aggressiveness. This genetic study demonstrated here is promising for implementing personalized strategies to screen for prostate cancer in diverse populations.

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“…Emerging evidence has demonstrated that PDLIMs are dysregulated in variety of tumors and are involved in various cellular and intercellular processes. For instance, PDLIM1 knockdown induces EMT and promotes invasion and metastasis in hepatocellular carcinoma (HCC) cells [ 36 ]; overexpression of PDLIM2 and PDLIM7 could serve as adverse prognostic factors for acute myeloid leukemia [ 37 ]; downregulation of PDLIM4 is correlated with aggressive tumor growth and poor prognosis in ovarian cancer patients [ 38 ]; PDLIM5 knockdown inhibited TGF β -signaling and TGF β -induced epithelial-mesenchymal transition [ 39 ]. However, to date, the association between PDLIM expression and clinicopathological features and prognosis of PRAD has not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

High Expression of PDLIM2 Predicts a Poor Prognosis in Prostate Cancer and Is Correlated with Epithelial-Mesenchymal Transition and Immune Cell Infiltration

Piao

Zheng

et al. 2022

Journal of Immunology Research

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Purpose. To elucidate the clinical and prognostic role of PDZ and LIM domain protein (PDLIM) genes and the association to epithelial-mesenchymal transition (EMT) and immune cell infiltration in patients with prostate cancer (PRAD). Methods. The data of RNA-seq, DNA methylation, and clinical features of PRAD patients were collected from The Cancer Genome Atlas (TCGA) database to define the prognostic value of PDLIM gene expression and the association with EMT and immune cell infiltration. A tissue microarray including 134 radical prostatectomy specimens was served as validation by immunohistochemistry (IHC) staining analysis. Results. The mRNA levels of PDLIM1/2/3/4/6/7 were significantly downregulated, while PDLIM5 was upregulated in PRAD ( P < 0.05 ). High expression of PDLIM2 mRNA suggests poor progression free interval in PRAD patients. DNA methylation of PDLIM2 was correlated with its mRNA expression level, and that the cg22973076 methylation site in PDLIM2 was associated with shorter PFI ( P < 0.05 ) in PRAD. Single-sample gene-set enrichment and gene functional enrichment results showed that PDLIM2 was correlated with EMT and immune processes. Spearman’s test showed a significant correlation with six reported EMT signatures and several EMT signature-related genes. Tumor microenvironment analysis revealed that the PDLIM2 mRNA expression was positively correlated with the immune score, stromal score, and various tumor infiltrating immune cells. Additionally, the results showed that patients in the high-PDLIM2 mRNA expression group may be more sensitive to immune checkpoint blockade therapy. Finally, IHC analysis further implicated the protein level of PDLIM2 was upregulated in PRAD and acts as a novel potential biomarker in predicting tumor progression. Conclusion. Our study suggests that PDLIM family genes might be significantly correlated with oncogenesis and the progression of PRAD. PDLIM2 correlated with EMT and immune cell infiltration by acting as an oncogene in PRAD, which may serve as a potential prognostic biomarker for PRAD patients.

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PDLIM5 inhibits STUB1-mediated degradation of SMAD3 and promotes the migration and invasion of lung cancer cells

Cited by 48 publications

References 49 publications

RAB26 contributes to the progression of non-small cell lung cancer after being transcriptionally activated by SMAD3

RAB26 contributes to the progression of non-small cell lung cancer after being transcriptionally activated by SMAD3

Correlation between Genomic Variants and Worldwide Epidemiology of Prostate Cancer

High Expression of PDLIM2 Predicts a Poor Prognosis in Prostate Cancer and Is Correlated with Epithelial-Mesenchymal Transition and Immune Cell Infiltration

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