LRG1 promotes proliferation and inhibits apoptosis in colorectal cancer cells via RUNX1 activation

Zhou, Ying; Zhang, Xintian; Zhang, Jingjing; Fang, Jing‐Yuan; Ge, Zhi‐Zheng; Li, Xiaobo

doi:10.1371/journal.pone.0175122

Cited by 60 publications

(69 citation statements)

References 38 publications

(33 reference statements)

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“…The LRG1 is a multipotent protein involved in positive regulation of angiogenesis, transforming growth factor receptor (TGF-βR) pathway signaling, and neutrophils degranulation. It is believed to be implicated in cell surveillance and regulation of apoptosis by down-regulation of cyclin D1 and apoptosis regulator Bcl-2 [49,51]. Although these findings may indicate that LRG1 can be one of the key points in promoting cell proliferation and inhibiting cell apoptosis, and given that up-regulation has been reported in several types of carcinoma, its exact role in CRC development and tumorigenesis remains poorly understood.…”

Section: Repercussion Of Proteins With Widely Proposed and Yet To Be mentioning

confidence: 99%

Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development

et al. 2020

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Background: Colorectal cancer (CRC) at a current clinical level is still hardly diagnosed, especially with regard to nascent tumors, which are typically asymptotic. Searching for reliable biomarkers of early diagnosis is an extremely essential task. Identification of specific post-translational modifications (PTM) may also significantly improve net benefits and tailor the process of CRC recognition. We examined depleted plasma samples obtained from 41 healthy volunteers and 28 patients with CRC at different stages to conduct comparative proteome-scaled analysis. The main goal of the study was to establish a constellation of protein markers in combination with their PTMs and semi-quantitative ratios that may support and realize the distinction of CRC until the disease has a poor clinical manifestation. Results: Proteomic analysis revealed 119 and 166 proteins for patients in stages I–II and III–IV, correspondingly. Plenty of proteins (44 proteins) reflected conditions of the immune response, lipid metabolism, and response to stress, but only a small portion of them were significant (p < 0.01) for distinguishing stages I–II of CRC. Among them, some cytokines (Clusterin (CLU), C4b-binding protein (C4BP), and CD59 glycoprotein (CD59), etc.) were the most prominent and the lectin pathway was specifically enhanced in patients with CRC. Significant alterations in Inter-alpha-trypsin inhibitor heavy chains (ITIH1, ITIH2, ITIH3, and ITIH4) levels were also observed due to their implication in tumor growth and the malignancy process. Other markers (Alpha-1-acid glycoprotein 2 (ORM2), Alpha-1B-glycoprotein (A1BG), Haptoglobin (HP), and Leucine-rich alpha-2-glycoprotein (LRG1), etc.) were found to create an ambiguous core involved in cancer development but also to exactly promote tumor progression in the early stages. Additionally, we identified post-translational modifications, which according to the literature are associated with the development of colorectal cancer, including kininogen 1 protein (T327-p), alpha-2-HS-glycoprotein (S138-p) and newly identified PTMs, i.e., vitamin D-binding protein (K75-ac and K370-ac) and plasma protease C1 inhibitor (Y294-p), which may also contribute and negatively impact on CRC progression. Conclusions: The contribution of cytokines and proteins of the extracellular matrix is the most significant factor in CRC development in the early stages. This can be concluded since tumor growth is tightly associated with chronic aseptic inflammation and concatenated malignancy related to loss of extracellular matrix stability. Due attention should be paid to Apolipoprotein E (APOE), Apolipoprotein C1 (APOC1), and Apolipoprotein B-100 (APOB) because of their impact on the malfunction of DNA repair and their capability to regulate mTOR and PI3K pathways. The contribution of the observed PTMs is still equivocal, but a significant decrease in the likelihood between modified and native proteins was not detected confidently.

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Section: Repercussion Of Proteins With Widely Proposed and Yet To Be mentioning

confidence: 99%

Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development

et al. 2020

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“…[4][5][6] For example, lncRNA CASC11 is up regulated in CRC and promotes growth and metastasis by interacting with hnRNP-K. 7 Likewise, lnc-GNAT1-1 is negatively associated with proliferation and metastasis processes in CRC. [9][10][11][12][13] Runt domain transcription factor (RUNX) family is mainly composed of RUNX1, RUNX2, RUNX, 14 and the functions of these three factors are slightly different. [9][10][11][12][13] Runt domain transcription factor (RUNX) family is mainly composed of RUNX1, RUNX2, RUNX, 14 and the functions of these three factors are slightly different.…”

mentioning

confidence: 99%

“…8 Many other important lncRNAs have also been confirmed to regulate growth and metastasis and influence the prognosis of CRC, such as lncRNA H19, lncRNA HOTAIR, lncRNA-NNT-AS1, lncRNA LINC01133, and lncRNA CCAT1 etc. [9][10][11][12][13] Runt domain transcription factor (RUNX) family is mainly composed of RUNX1, RUNX2, RUNX, 14 and the functions of these three factors are slightly different. It has been widely accepted that RUNX1 plays a vital role in haematopoiesis and haematopoietic function.…”

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confidence: 99%

Long non‐coding RNA RUNX1‐IT1 plays a tumour‐suppressive role in colorectal cancer by inhibiting cell proliferation and migration

Shi

Zhong

Song

et al. 2018

Cell Biochemistry & Function

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Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in the progression of various cancers. In this study, we aim to investigate the role of lncRNA RUNX1-IT1 in the development of colorectal cancer (CRC). The expression levels of lncRNA RUNX1-IT1 were measured using quantitative real-time Polymerase Chain Reaction(qRT-PCR). CCK8 proliferation assay, transwell assay, and flow cytometry were performed to evaluate the effect of lncRNA RUNX1-IT1 on CRC cell proliferation, migration, and apoptosis. The proliferation markers (PCNA, Ki67), apoptosis markers (cleaved-PARP, cleaved-caspase3), and MMP9 are detected by western blotting. Significant down regulation of lncRNA RUNX1-IT1 was measured in CRC tissues and three CRC cell lines (HCT116, HT29, and RKO) compared with paired nontumorous adjacent tissues (P < 0.01) or the normal colonic epithelial cell line FHC (P < 0.05), respectively. Moreover, the proliferative and migration potential of CRC cells were inhibited by overexpressing lncRNA RUNX1-IT1, which could be obviously improved by knocking down lncRNA RUNX1-IT1. The protein levels of PCNA, Ki67, and MMP9 were upregulated by overexpressing lncRNA RUNX1-IT1 and down regulated in si-RUNX1-IT1 cells.Besides, lncRNA RUNX1-IT1 could also promote the apoptosis of CRC cells. In conclusion, lncRNA RUNX1-IT1 is downregulated in CRC and plays a tumour-suppressive role due to the regulatory of cell proliferation, migration, and apoptosis. Significance of the study:We demonstrated that lncRNA RUNX1-IT1 was down regulated both in CRC tissues and cell lines. Besides, lncRNA RUNX1-IT1 could serve as a potential diagnostic biomarker and play a tumour-suppressive role owing to its good diagnostic efficacy and inhibition of CRC cell proliferation and migration.

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“…Silencing RUNX1 inhibited cellar proliferation and promoted of apoptosis [24]. miR-141 can retard cell proliferation and migration.…”

Section: Discussionmentioning

confidence: 98%

CircMUC16 promotes autophagy of epithelial ovarian cancer via interaction with ATG13 and miR-199a

et al. 2020

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Background: Circular RNA (circRNA) has been proven to play a significant role in multiple types of cancer. However, the expression and role of circRNAs in epithelial ovarian cancer (EOC) remains elusive. Methods: CircRNA and mRNA expression profiles of EOC were screened with sequencing analysis. Gene silencing and over-expression were used to study circRNA function. Cell proliferation and Matrigel invasion assays were used to detect cell proliferation and invasion, respectively. The expression of circRNAs, mRNAs and miRNAs was detected using qPCR. The location of circRNAs was detected using FISH. The expression of proteins was detected using western blot and immunohistochemistry. Results: CircMUC16 had increased expression in EOC tissues as compared to healthy ovarian tissues. The expression of circMUC16 was linked to the progression in stage and grade of EOC. Hence, silencing circMUC16 suppressed autophagy flux of SKOV3 cells. In contrast, ectopic expression of circMUC16 promoted autophagy flux of A2780 cells. CircMUC16-mediated autophagy exacerbated EOC invasion and metastasis. Mechanistically, circMUC16 could directly bind to miR-199a-5p and relieve suppression of target Beclin1 and RUNX1. In turn, RUNX1 elevated the expression of circMUC16 via promotion of its transcription. CircMUC16 could directly bind to ATG13 and promote its expression. Conclusion: This study demonstrated that circMUC16 regulated Beclin1 and RUNX1 by sponging miR-199a-5p. The data suggested that circMUC16 could be a potential target for EOC diagnosis and therapy.

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LRG1 promotes proliferation and inhibits apoptosis in colorectal cancer cells via RUNX1 activation

Cited by 60 publications

References 38 publications

Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development

Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development

Long non‐coding RNA RUNX1‐IT1 plays a tumour‐suppressive role in colorectal cancer by inhibiting cell proliferation and migration

CircMUC16 promotes autophagy of epithelial ovarian cancer via interaction with ATG13 and miR-199a

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