LpCat1 Promotes Malignant Transformation of Hepatocellular Carcinoma Cells by Directly Suppressing STAT1

Ji, Weidan; Zhang, Peng; Sun, Bin; Chen, Lei; Zhang, Qin; Guo, Minggao; Su, Changqing

doi:10.3389/fonc.2021.678714

Cited by 14 publications

(16 citation statements)

References 37 publications

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“…Further experiments in vivo should be performed to explore the role of nectin-1 in the metastasis of hepatocellular carcinoma in an animal model. The relationship between the levels of nectin-1 and the prognosis of patients with HCC at different stages should also be analyzed ( 40 , 41 ).…”

Section: Discussionmentioning

confidence: 99%

High expression of nectin-1 indicates a poor prognosis and promotes metastasis in hepatocellular carcinoma

Wang

Xing²,

Chen³

et al. 2022

Front. Oncol.

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ObjectivesNectins are a new class of cell-adhesion molecules that play an important role in tumorigenesis and disease progression. The aim of this study was to investigate the prognostic and pathogenetic roles of nectins in hepatocellular carcinoma (HCC).MethodsThe expression levels of the nectin family in HCC and their role in prognosis were analyzed by bioinformatics analysis based on The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma database. The correlations between nectins and immune cells were analyzed using TIMER. The functional enrichment of the nectin-1 coexpression network was evaluated in TCGA cohort, and the expression levels of nectin-1 were detected by immunohistochemistry and Western blot analysis. A Transwell kit was used for cell migration experiments. Cell proliferation was analyzed using Cell Counting Kit-8.ResultsThe expression levels of nectin-1 protein in the cancer tissues of 28 patients with HCC were higher than those in paracancerous tissues. The Kaplan–Meier plotter analysis showed that the high expression of all nectin family numbers was related to the poor prognosis of HCC patients. The abnormal expression of nectin-1 effectively distinguished the prognosis at different stages and grades of HCC. The high expression of 17 methylation sites of the nectin-1 gene was related to the high overall survival of HCC patients. Kyoto Encyclopedia of Genes and Genomes analysis of genes negatively correlated with nectin-1, revealing their close relation to the regulation of the immune-effector process. Pearson’s correlation analysis showed that nectin-1 was significantly positively correlated with multiple immune genes and B cells, CD4+ T cells, macrophages, neutrophils, and dendritic cell infiltration. Cell proliferation of the knockdown (KD) group decreased significantly compared to the NC-KD group. The number of metastatic cells in the KD group decreased significantly compared to that in the NC-KD group.ConclusionsAbnormal expression of nectins and multiple methylation sites closely correlates with poor prognosis in HCC patients. Nectins are related to immune cell infiltration and immune-related genes. In particular, nectin-1 can promote the proliferation and migration of liver cancer cells and distinguish the prognosis at different stages and grades of HCC. Nectin-1 might be a new potential molecular marker for prognostic evaluation and also a therapeutic target for HCC.

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Section: Discussionmentioning

confidence: 99%

High expression of nectin-1 indicates a poor prognosis and promotes metastasis in hepatocellular carcinoma

Wang

Xing²,

Chen³

et al. 2022

Front. Oncol.

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“…LPCAT1 was found to contribute to cutaneous squamous cell carcinoma progression through EGFR-mediated protein kinase B and p38MAPK signaling pathways [ 24 ]. High-LPCAT1 expression could inhibit STAT1 expression, up-regulate CyclinD1, CyclinE, CDK4 and MMP-9, and decrease p27kip1 to promote cancer progression in HCC [ 25 ]. More knowledge is needed to understand how LPCAT1 promotes tumorigenesis in HCC.…”

Section: Discussionmentioning

confidence: 99%

LPCAT1 acts as an independent prognostic biomarker correlated with immune infiltration in hepatocellular carcinoma

Wang

Ding

et al. 2022

Eur J Med Res

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Background Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is overexpressed in multiple human tumors. However, the role of LPCAT1 in hepatocellular carcinoma (HCC) has not been understood. We aim to explore the relationships between LPCAT1 expression and prognosis, clinicopathological features, tumor microenvironment (TME), immune cell infiltration, immune checkpoint gene expression, and related signaling pathways in HCC. Furthermore, we also explored the relationship between LPCAT1 expression and drug sensitivity to HCC treatment. Methods The expression profiles were acquired from the Cancer Genome Atlas (TCGA) and the Human Protein Atlas (THPA). Immune status and infiltration in cancer tissues were explored using the single sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithm. Results LPCAT1 was overexpressed in HCC, and its expression was related to poor prognosis, LPCAT1 was an independent prognostic biomarker in HCC. Expression of LPCAT1 increased statistically with the increase of clinical stage and grade of HCC patients. GO and KEGG network analysis revealed that LPCAT1 positively associated molecules were mostly enriched in functions related to cell adhesion. The TME score of high-LPCAT1 group was significantly higher than that of low-LPCAT1 group. Immune infiltrating cells positively correlated with LPCAT1 expression were Macrophages M0, B cells memory, Dendritic cells activated, T cells regulatory and T cells gamma delta in HCC. We found a positive correlation between LPCAT1 and most immune checkpoint gene expression. The IC50 of 5-Fluorouracil, Gemcitabine, Mitomycin C, Sorafenib and Cabozantinib in patients with high-LPCAT1 expression was lower than that in patients with low-LPCAT1 expression. Our findings provide a wealth of information for further understanding of the biological functions and signaling pathways of LPCAT1 in HCC. Conclusions LPCAT1 is an independent prognostic biomarker and associated with tumor microenvironment, immune cell infiltration, immune checkpoint expression and drug sensitivity in hepatocellular carcinoma.

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“…Upregulation of LPCAT1 was found in numerous solid cancers and was correlated with multiple tumor malignant characteristics including progression, metastasis, recurrence and poor prognosis by promoting epithelial-mesenchymal transition, tumor microenvironment, tumor immune infiltration and chemoresistance [11][12][13][14][15][16][17][18][19][20][21][22][23][24]. Mechanistically, LPCAT1 inhibited tumor suppressor gene STAT1 expression, up-regulated Cyclins to promote HCC progression [14]. Furthermore, LPCAT1 promoted disease progression via accelerating epithelial-mesenchymal transition by activating Wnt/b-catenin signaling pathway in hepatocellular carcinoma [16].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, LPCAT1 has been reported to contribute to cancer initiation and progression in various cancer types. Upregulation of LPCAT1 was found in numerous solid cancers and was correlated with multiple tumor malignant characteristics including progression, metastasis, recurrence and poor prognosis by promoting epithelial-mesenchymal transition, tumor microenvironment, tumor immune infiltration and chemoresistance [11][12][13][14][15][16][17][18][19][20][21][22][23][24]. Mechanistically, LPCAT1 inhibited tumor suppressor gene STAT1 expression, up-regulated Cyclins to promote HCC progression [14].…”

Section: Discussionmentioning

confidence: 99%

“…Among these members, LPCAT1 has attracted much attention in a variety of cancers. So far, LPCAT1 has been found to be overexpressed in various solid cancers including prostate cancer [11], hepatocellular carcinoma [12][13][14][15][16], breast cancer [17,18], endometrial cancer [19], oral squamous cell carcinoma [20], esophageal squamous cell carcinoma [21], cutaneous squamous cell carcinoma [22], lung adenocarcinoma [23,24] and its overexpression promoted the progression, metastasis, recurrence and worsened survival of these solid cancers. However, the pattern of LPCAT1 expression and its clinical relevance have been rarely studied in AML.…”

Section: Introductionmentioning

confidence: 99%

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Clinical significance of down-regulated LPCAT1 expression in acute myeloid leukemia

Chen

Lin

et al. 2022

Preprint

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Background Lysophosphatidylcholine acyltransferase 1 (LPCAT1) overexpression has been found in various solid cancers and promoted the progression, metastasis, and recurrence of these diseases. However, the expression pattern of LPCAT1 in acute myeloid leukemia was unclear. This study aimed to assess expression status of LPCAT1 and its clinical relevance in acute myeloid leukemia (AML). Methods and Results LPCAT1 expression was significant lower in AML than controls predicted by public databases. Also, a significantly down-regulated of LPCAT1 of bone marrow in AML compared with controls was validated by real-time quantitative PCR (RQ-PCR) [0.056 (0.000-0.846) vs 0.253 (0.031-1.000)]. The DiseaseMeth version 2.0 and The Cancer Genome Atlas analysis showed LPCAT1 promoter was hypermethylated in AML and a strongly negative correlation was found between LPCAT1 expression and methylation (R=-0.610, P<0.001). RQ-PCR revealed the frequency of LPCAT1 low-expression in FAB-M4/M5 subtype was lower than other subtypes (P=0.018). The ROC curve revealed LPCAT1 expression might serve as a potential diagnostic marker for differentiating AML from normal with an area under the ROC curve of 0.819 (95% CI 0.743-0.894, P<0.001). In cytogenetically normal AML, the overall survival in patients with LPCAT1 low-expression was significantly longer than that in those without LPCAT1 low-expressed group (median 19 versus 5.5 months, P=0.036). Conclusion LPCAT1 is downregulated in bone marrow and LPCAT1 expression can be as a potential biomarker for diagnosis and evaluating prognosis in AML.

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LpCat1 Promotes Malignant Transformation of Hepatocellular Carcinoma Cells by Directly Suppressing STAT1

Cited by 14 publications

References 37 publications

High expression of nectin-1 indicates a poor prognosis and promotes metastasis in hepatocellular carcinoma

High expression of nectin-1 indicates a poor prognosis and promotes metastasis in hepatocellular carcinoma

LPCAT1 acts as an independent prognostic biomarker correlated with immune infiltration in hepatocellular carcinoma

Clinical significance of down-regulated LPCAT1 expression in acute myeloid leukemia

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