Identification of low abundance proteins in colorectal cancer tissues

Lim, Shi Rou; Gooi, Boon-Hui; Gam, Lay‐Harn

doi:10.3233/cbm-130307

Cited by 3 publications

(2 citation statements)

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“…The expression of LRRN4 was high in CRC and was correlated with pathological stage and OS status in the TCGA cohort and our cohort. However, a previous study found that LRRN4 was of low abundance in normal colon tissue and that the level of LRRN4 was much lower in CRC tissue, which was detected by coupling hydroxyapatite chromatography and SDS-PAGE followed by mass spectrometry analysis [ 18 ]. In fact, in a few cases, we also found that the expression of LRRN4 is higher in normal tissues than in tumors.…”

Section: Discussionmentioning

confidence: 99%

“…LRRN4 has been identified as a marker of primary mesothelial cells, while it was found to be either nondetectable or downregulated in mesothelioma [ 17 ]. Although LRRN4 was not highly expressed in normal colon tissue, the level of LRRN4 was much lower in CRC tissue, as detected by the coupling methods of hydroxyapatite chromatography and SDS–PAGE followed by mass spectrometry analysis [ 18 ]. However, the clinical significance of LRRN4 remains to be clarified by investigation in a larger sample.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic value and biological function of LRRN4 in colorectal cancer

Chen

Long

et al. 2022

Cancer Cell Int

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Background Several nervous and nerve-related biomarkers have been detected in colorectal cancer (CRC) and can contribute to the progression of CRC. However, the role of leucine-rich repeat neuronal 4 (LRRN4), a recently identified neurogenic marker, in CRC remains unclear. Methods We examined the expression and clinical outcomes of LRRN4 in CRC from TCGA-COREAD mRNA-sequencing datasets and immunohistochemistry in a Chinese cohort. Furthermore, colony formation, flow cytometry, wound healing assays and mouse xenograft models were used to investigate the biological significance of LRRN4 in CRC cell lines with LRRN4 knockdown or overexpression in vitro and in vivo. In addition, weighted coexpression network analysis, DAVID and western blot analysis were used to explore the potential molecular mechanism. Results We provide the first evidence that LRRN4 expression, at both the mRNA and protein levels, was remarkably high in CRC compared to controls and positively correlated with the clinical outcome of CRC patients. Specifically, LRRN4 was an independent prognostic factor for progression-free survival and overall survival in CRC patients. Further functional experiments showed that LRRN4 promoted cell proliferation, cell DNA synthesis and cell migration and inhibited apoptosis. Knockdown of LRRN4 can correspondingly decrease these effects in vitro and can significantly suppress the growth of xenografts. Several biological functions and signaling pathways were regulated by LRRN4, including proteoglycans in cancer, glutamatergic synapse, Ras, MAPK and PI3K. LRRN4 knockdown resulted in downregulation of Akt, p-Akt, ERK1/2 and p-ERK1/2, the downstream of the Ras/MAPK signaling pathway, overexpression of LRRN4 leaded to the upregulation of these proteins. Conclusions Our results suggest that LRRN4 could be a biological and molecular determinant to stratify CRC patients into distinct risk categories, and mechanistically, this is likely attributable to LRRN4 regulating several malignant phenotypes of neoplastic cells via RAS/MAPK signal pathways.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prognostic value and biological function of LRRN4 in colorectal cancer

Chen

Long

et al. 2022

Cancer Cell Int

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Intracellular metal enhanced fluorescence utilizing gold nanoparticles embedded in hydrogel droplets for sensitive protein detection in cells

Sebben,

2023

Talanta Open

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A promising naphthoquinone [8-hydroxy-2-(2-thienylcarbonyl)naphtho[2,3-b]thiophene-4,9-dione] exerts anti-colorectal cancer activity through ferroptosis and inhibition of MAPK signaling pathway based on RNA sequencing

et al. 2020

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Naphthoquinones are naturally occurring metabolites with recognized anti-cancer potential but limited clinical application. This study investigated the molecular mechanism of 8-hydroxy-2-(2-thenoyl)naphtho[2,3-b]thiophene-4,9-dione (1), a new candidate for colorectal cancer (CRC) treatment, using different experimental settings: MTT, clonogenic, wound healing, and cell cycle assays; as well as RNA sequencing. Naphthoquinone 1 selectively reduced the viability and migration of HT-29 cells by G2/M arrest and changes in their transcriptome signature with significant effect on cellular survival, proliferation, angiogenesis, response to interferon, oxidative stress, and immune response. Impact analysis identified ferroptosis and MAPK pathways as significantly affected. In summary, our results suggest that 1 induces the selective death of CRC cells by inducing oxidative stress, ferroptosis, and MAPK inhibition.

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Identification of low abundance proteins in colorectal cancer tissues

Abstract: The proteins were isolated from the cancerous tissues as either up-regulated or down-regulated proteins as compared to normal tissues and therefore may play important roles in cancer development.

Cited by 3 publications

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Prognostic value and biological function of LRRN4 in colorectal cancer

Prognostic value and biological function of LRRN4 in colorectal cancer

Intracellular metal enhanced fluorescence utilizing gold nanoparticles embedded in hydrogel droplets for sensitive protein detection in cells

A promising naphthoquinone [8-hydroxy-2-(2-thienylcarbonyl)naphtho[2,3-b]thiophene-4,9-dione] exerts anti-colorectal cancer activity through ferroptosis and inhibition of MAPK signaling pathway based on RNA sequencing

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