Hypoxia‐induced cofilin 1 promotes hepatocellular carcinoma progression by regulating the PLD1/AKT pathway

Yao, Bowen; Li, Yazhao; Chen, Tianxiang; Niu, Yongshen; Wang, Yufeng; Yang, Yuanyuan; Wei, Xinyu; Liu, Qingguang; Tu, Kangsheng

doi:10.1002/ctm2.366

Cited by 44 publications

(28 citation statements)

References 41 publications

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“…In this study, the expression of vimentin was significantly decreased and that of E‐cadherin was increased in PC‐11 and PC‐40 cells, indicating that knockout of PLD1 could attenuate EMT progression in CASKI cells, and this phenomenon was observed in mouse tumour tissues in vivo. Previous studies demonstrated that inhibition of PLD1 could attenuate tumour EMT in hepatocellular carcinoma mice, 21 and PLD1 mediated EMT in hepatocellular carcinoma 24 …”

Section: Discussionmentioning

confidence: 95%

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Phospholipase D1 promotes cervical cancer progression by activating the RAS pathway

Song

Meng

Jiang

et al. 2022

J Cellular Molecular Medi

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This study aimed to further investigate the effect of PLD1 on the biological characteristics of human cervical cancer (CC) cell line, CASKI and the potential related molecular mechanism. CRISPR/Cas9 genome editing technology was used to knock out the PLD1 gene in CASKI cells. Cell function assays were performed to evaluate the effect of PLD1 on the biological function of CASKI cells in vivo and in vitro. A PLD1‐overexpression rescue experiment in these knockout cells was performed to further confirm its function. Two PLD1‐knockout CASKI cell lines (named PC‐11 and PC‐40, which carried the ins1/del4 mutation and del1/del2/ins1 mutation, respectively), were constructed by CRISPR/Cas9. PLD1 was overexpressed in these knockout cells (named PC11‐PLD1 and PC40‐PLD1 cells), which rescued the expression of PLD1 by approximately 71.33% and 74.54%, respectively. In vivo, the cell function assay results revealed that compared with wild‐type (WT)‐CASKI cells, the ability of PC‐11 and PC‐40 cells to proliferate, invade and migrate was significantly inhibited. The expression of H‐Ras and phosphorylation of Erk1/2 (p‐Erk1/2) was decreased in PC‐11 and PC‐40 cells compared with WT‐CASKI cells. PC‐11 and PC‐40 cells could sensitize CASKI cells to cisplatin. More importantly, the proliferation, migration and invasion of PC11‐PLD1 and PC40‐PLD1 cells with PLD1 overexpression were significantly improved compared with those of the two types of PLD1 knockout cells. The sensitivity to cisplatin was decreased in PC11‐PLD1 and PC40‐PLD1 cells compared with PC‐11 and PC‐40 cells. In vivo, in the PC‐11 and PC‐40 tumour groups, tumour growth was significantly inhibited and tumour weight (0.95 ± 0.27 g and 0.66 ± 0.43 g vs. 1.59 ± 0.67 g, p = 0.0313 and 0.0108) and volume (1069.41 ± 393.84 and 1077.72 mm3 ± 815.07 vs. 2142.94 ± 577.37 mm3, p = 0.0153 and 0.0128) were significantly reduced compared to those in the WT‐CASKI group. Tumour differentiation of the PC‐11 and PC40 cells was significantly better than that of the WT‐CASKI cells. The immunohistochemistry results confirmed that the expression of H‐Ras and p‐Erk1/2 was decreased in PC‐11 and PC‐40 tumour tissues compared with WT‐CASKI tumour tissues. PLD1 promotes CC progression by activating the RAS pathway. Inhibition of PLD1 may serve as an attractive therapeutic modality for CC.

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Section: Discussionmentioning

confidence: 95%

“…Previous studies demonstrated that inhibition of PLD1 could attenuate tumour EMT in hepatocellular carcinoma mice, 21 and PLD1 mediated EMT in hepatocellular carcinoma. 24 The RAS/RAF/MEK/ERK (MAPK) signalling pathway is pivotal in the cell signalling cascade that regulates cell survival, growth, migration and invasion. 25…”

Section: Discussionmentioning

confidence: 99%

Phospholipase D1 promotes cervical cancer progression by activating the RAS pathway

Song

Meng

Jiang

et al. 2022

J Cellular Molecular Medi

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“…According to many previous studies, CFL1 has promiscuous physiological effects, including cell motility, cell apoptosis and lipid metabolism (8). Currently, many researches showed the pivotal role of CFL1 in the development of tumor (9,10). CFL1 was higher in tumor than paired-normal tissue, including pancreatic cancer, vulvar squamous cell carcinoma, hepatocellular carcinoma, esophagus cancer, and prostate cancer (7,(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Cofilin1 Is a Poorer Prognostic Biomarker and potential Immunotherapy in Systematic Pan-Cancer

Yang

Qiu

Zhong

et al. 2022

Preprint

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Background: Cofilin1(CFL1) is an actin-binding protein that can impact the prognosis of patients with malignant cancer through different mechanisms. However, the CFL1 and pan-cancer correlation are unclear. The current research aims studying the link between CFL1 expression and tumor microenvironment and exploring this mechanism in pan-cancer. Methods: To assess the CFL1 expression in diverse cancer types when compared to normal tissues, the Oncomine database was utilized. The link between CFL1 expression and clinical prognosis was estimated by Kaplan-Meier Plotter. To evaluate the connection between CFL1, immune infiltration and related gene maker sets, the TIMER database was utilized. CFL1 was further committed to enrichment analysis for the KEGG pathway. Results: The expression level of CFL1 gene is heterogeneous in different cancer cell lines. The high expression of CFL1 makes pan-cancer patients have poor survival benefits, excluding THYM(Thymoma) patients. The correlation between CFL1 and immune cells was different among cancer types, as proved. The CFL1 expression was linked to TMB and MSI within 14 and six cancer types, respectively. The majority of genes related to immunity and co-expressed with CFL1 has a positive correlation in most tumors. Finally, GSEA analysis shows that CFL1 impact the pathway of metabolism. Conclusion: The study results showed that CFL1 could be a latent prognostic biomarker as well as possible immunotherapy in pan-cancers.

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“…Previous study has demonstrated that HCC is the most serious tumor of hypoxia [ 9 ]. Abundant evidence is showing that hypoxia can induce an increase in tumor malignancy, including tumor progression, invasion and metastasis, contributing to poor prognosis in HCC [ 10 , 11 ]. Nowadays immune checkpoint inhibitors (ICI) have become an effective immunotherapy and are popularly used in the treatment of HCC [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

8DEstablishment and validation of a hypoxia-related signature predicting prognosis in hepatocellular carcinoma

2021

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Background Hypoxia plays a crucial role in immunotherapy of hepatocellular carcinoma (HCC) by changing the tumor microenvironment. Until now the association between hypoxia genes and prognosis of HCC remains obscure. We attempt to construct a hypoxia model to predict the prognosis in HCC. Results We screened out 3 hypoxia genes (ENO1, UGP2, TPI1) to make the model, which can predict prognosis in HCC. And this model emerges as an independent prognostic factor for HCC. A Nomogram was drawn to evaluate the overall survival in a more accurate way. Furthermore, immune infiltration state and immunosuppressive microenvironment of the tumor were detected in high-risk patients. Conclusion We establish and validate a risk prognostic model developed by 3 hypoxia genes, which could effectively evaluate the prognosis of HCC patients. This prognostic model can be used as a guidance for hypoxia modification in HCC patients undergoing immunotherapy.

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Hypoxia‐induced cofilin 1 promotes hepatocellular carcinoma progression by regulating the PLD1/AKT pathway

Abstract: 1. Cofilin 1 is overexpressed in HCC, especially in PVTT tissues. 2. Cofilin 1 is up-regulated in hypoxia condition and promotes HCC progression. 3. CFL1 binds to PLD1 and maintains PLD1 protein stability. 4. HIF-1α regulates CFL1 transcription and activates CFL1-PLD1-AKT axis in HCC.

Cited by 44 publications

References 41 publications

Phospholipase D1 promotes cervical cancer progression by activating the RAS pathway

Phospholipase D1 promotes cervical cancer progression by activating the RAS pathway

Cofilin1 Is a Poorer Prognostic Biomarker and potential Immunotherapy in Systematic Pan-Cancer

8DEstablishment and validation of a hypoxia-related signature predicting prognosis in hepatocellular carcinoma

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