LMNA functions as an oncogene in hepatocellular carcinoma by regulating the proliferation and migration ability

Liu, Heng; Li, Dongming; Kan, Shuang; He, Guozhang; Zhou, Kun; Wang, Liping; Chen, Ming; Shu, Wei

doi:10.1111/jcmm.15829

Cited by 21 publications

(20 citation statements)

References 38 publications

(61 reference statements)

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“…In agreement with these works, in previous papers we also found that LMNA expression was related to a less malignant phenotype in human neuroblastoma [23,26]. By contrast, some studies revealed a link between increased LMNA expression and tumor progression in colorectal, prostate, ovarian and hepatocellular cancers [14,[31][32][33]. This ambiguity in the LMNA gene role as a cancer biomarker is probably due to the numerous diverse functions that Lamins perform in the cell and their variable expression between cancer subtypes [13].…”

Section: Discussionsupporting

confidence: 88%

Role of Lamin A/C as Candidate Biomarker of Aggressiveness and Tumorigenicity in Glioblastoma Multiforme

et al. 2021

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Nuclear lamina components have long been regarded as scaffolding proteins, forming a dense fibrillar structure necessary for the maintenance of the nucleus shape in all the animal kingdom. More recently, mutations, aberrant localisation and deregulation of these proteins have been linked to several diseases, including cancer. Using publicly available data we found that the increased expression levels of the nuclear protein Lamin A/C correlate with a reduced overall survival in The Cancer Genome Atlas Research Network (TCGA) patients affected by glioblastoma multiforme (GBM). We show that the expression of the LMNA gene is linked to the enrichment of cancer-related pathways, particularly pathways related to cell adhesion and cell migration. Mimicking the modulation of LMNA in a GBM preclinical cancer model, we confirmed both in vitro and in vivo that the increased expression of LMNA is associated with an increased aggressiveness and tumorigenicity. In addition, delving into the possible mechanism behind LMNA-induced GBM aggressiveness and tumorigenicity, we found that the mTORC2 component, Rictor, plays a central role in mediating these effects.

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Section: Discussionsupporting

confidence: 88%

Role of Lamin A/C as Candidate Biomarker of Aggressiveness and Tumorigenicity in Glioblastoma Multiforme

et al. 2021

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“…44,45 Cells with low levels of lamin A have flexible nucleus and could easily compress through juxtaposed cells during migration; hence, the levels of lamin A in the nucleus is crucial to eventually ensure successful migration and cell survival. 46,47 Liu et al 48 showed that the migration ability of LMNA knockout cell lines in hepatocellular carcinoma (HCC) was significantly lower than that of the wild-type cells. Moreover, according to the authors, the LMNA gene was abnormally expressed in distinct cancer types and the survival rate of the HCC patients with a high expression of the LMNA gene was significantly reduced compared with the rate in patients with a low LMNA expression.…”

Section: Protein Relocation and Nuclear Proteins In The Secretome Of Tumoral Cellsmentioning

confidence: 99%

Bioinformatic reanalysis of public proteomics data reveals that nuclear proteins are recurrent in cancer secretomes

Morais

Zelanis

2021

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Proteins secreted by tumoral cells (cancer secretomes) have been continuously associated with cancer development and progression processes. In this context, secreted proteins contribute to the signaling mechanisms related to tumor growth and spreading and studies on tumor secretomes provide valuable clues on putative tumor biomarkers.Although the in vitro identification of intracellular proteins in cancer secretome studies has usually been associated with contamination derived from cell lysis or fetal bovine serum, accumulated evidence reports on intracellular proteins with moonlighting functions in the extracellular environment. In this study, we performed a systematic reanalysis of public proteomics data regarding different cancer secretomes, aiming to identify intracellular proteins potentially secreted by tumor cells via unconventional secretion pathways. We found a similar repertoire of unconventionally secreted proteins, including the recurrent identification of nuclear proteins secreted by different cancer cells. In addition, in some cancer types, immunohistochemical data were in line with proteomics identifications and suggested that nuclear proteins might relocate from the nucleus to the cytoplasm. Both the presence of nuclear proteins and the likely unconventional secretion of such proteins may comprise biological signatures of malignant transformation in distinct cancer types and may be targeted for further analysis aiming at the prognostic/ therapeutic value of such features.

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“…By subtyping analysis, to validate subtype biomarkers in HCC it was found up regulation of HSPA6 (heat shock proteins) associate with hepatocellular carcinoma and LMNA gene due to proliferation and migration ability function as an oncogene in HCC[31]. PPA2 which modulates histone methylation that interferes with p-53 induced apoptosis can be a marker gene for HCC.…”

Section: Discussionmentioning

confidence: 99%

Single-Cell Transcriptome Analysis Identifies Novel Biomarkers Involved in Major Liver Cancer Subtypes

Swain

Pandey

Sera

et al. 2022

Preprint

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Liver cancers including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are leading cause of death worldwide. Single-cell transcriptomics studies have vast potential in advancing our understanding of cancers by defining the cellular composition of different solid tumor types. We peformed an integrated analysis using single-cell RNA sequencing (scRNA-seq) data from cancerous and healthy liver tissues in order to identify the molecular progression and intercellular heterogeneity across cell types in the liver cancer. Moreover, we performed a subtype specific analyses, separately for HCC and ICC, to identify any molecular drivers uniquely associated with these liver cancers. The scRNA-seq dataset comprising 5 healthy controls and 19 liver cancer patients were collected from Human Cell Atlas and Gene Expression Omnibus (GEO), respectively. Our analyses confirmed upregulation of four previously known malignant cell marker genes, namely, EPCAM, KRT19, KRT7 and S100P in the cancerous liver cells. Of these, KRT7 gene has been reported to be associated with ovarian cancer in the past studies. Noteworthy, four marker genes specific to the G1/S (MCM5 and PCNA) and G2/M phases (HMGB2 and CKS2) of the cell cycle were upregulated in the cancerous liver cells. This indicates that these four marker genes are actively dividing in these two phases in cancerous cells as compared to normal liver cells. Our differential expression analysis identified 2 upregulated genes (ATF3 and S100A11) and 2 downregulated genes (FCN3 and FGB) in the liver cancer. Our subtype based differential expression analysis identified 4 genes (HSPA6, LMNA, ATP1B1 and DCXR) specific to HCC and 3 genes (HSPB1, APOC3 and APOA1) specific to ICC. CD4+ T-cell, Hepatocyte, neutrophil, mesenchymal cells and liver bud hepatic cells are the predominant cell-types in liver cells. Our scRNA-seq study revealed the mesenchymal cells as potential malignant cell types in liver cancers. Our work suggests future research on developing liver cancer subtypes therapies could target these cell types and associated molecular markers.

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LMNA functions as an oncogene in hepatocellular carcinoma by regulating the proliferation and migration ability

Cited by 21 publications

References 38 publications

Role of Lamin A/C as Candidate Biomarker of Aggressiveness and Tumorigenicity in Glioblastoma Multiforme

Role of Lamin A/C as Candidate Biomarker of Aggressiveness and Tumorigenicity in Glioblastoma Multiforme

Bioinformatic reanalysis of public proteomics data reveals that nuclear proteins are recurrent in cancer secretomes

Single-Cell Transcriptome Analysis Identifies Novel Biomarkers Involved in Major Liver Cancer Subtypes

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