MiR-103a promotes tumour growth and influences glucose metabolism in hepatocellular carcinoma

Liu, Yuling; Zhang, Yuanzhou; Xiao, Bowen; Hu, Jun; Liang, Shunshun; Pang, Yu; Xu, Haoping; Ao, Junping; Yang, Juan; Liang, Xiaofei; Wei, Lin; Wang, Yunfeng; Luo, Xiaoying

doi:10.1038/s41419-021-03905-3

Cited by 18 publications

(12 citation statements)

References 44 publications

(40 reference statements)

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“…This study is the first to comprehensively analyze the role and molecular mechanism of miR-103a-3p-EVA1A interplay in HCC growth and metastasis. In HCC tissues and cell lines, we confirmed that the expression of EVA1A is downregulated, and the expression of miR-103a-3p in HCC tissues and cells is upregulated, which is consistent with previous studies [ 35 – 37 ]. We also analyzed the correlation of miR-103a-3p expression with HCC tumor stages and its prognostic prediction value and found that high miR-103a-3p expression was positively correlated with poor overall survival, so miR-103a-3p could serve as a potential biomarker and a prognostic factor for poor outcome in patients with HCC.…”

Section: Discussionsupporting

confidence: 92%

Down-regulation of EVA1A by miR-103a-3p promotes hepatocellular carcinoma cells proliferation and migration

Liao

Gong

et al. 2022

Cell Mol Biol Lett

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Background EVA1A (Eva-1 homolog A), a novel protein involved in autophagy and apoptosis, functions as a tumor suppressor in some human primary cancers, including hepatocellular carcinoma (HCC). While it is consistently downregulated in several cancers, its involvement in hepatocarcinogenesis is still largely unknown. Methods We first detected the expression of EVA1A in HCC tissues and cell lines using RT‒qPCR, immunohistochemistry and western blotting and detected the expression of miR-103a-3p by RT‒qPCR. Then, bioinformatics prediction, dual-luciferase reporter gene assays and western blotting were used to screen and identify the upstream microRNA of EVA1A. After manipulating the expression of miR-103a-3p or EVA1A, wound healing, invasion, proliferation, colony formation, apoptosis, autophagy, mitosis and mitochondrial function assays, including mitochondrial membrane potential, ROS and ATP production assays, were performed to investigate the functions of miR-103a-3p targeting EVA1A in HCC cells. Apoptosis-related proteins were assessed by RT‒qPCR (TP53) or western blotting (TP53, BAX, Bcl-2 and caspase-3). Autophagy level was evaluated by observing LC3 puncta and examining the protein levels of p62, Beclin1 and LC3-II/I. Results We found that EVA1A expression was decreased while miR-103a-3p expression was increased in HCC tissues and cell lines and that their expression was inversely correlated in HCC patients. The expression of miR-103a-3p was associated with HCC tumor stage and poor prognosis. miR-103a-3p could target EVA1A through direct binding to its 3'-UTR and suppress its expression. Overexpression of miR-103a-3p significantly downregulated the expression of EVA1A, TP53 and BAX, upregulated the JAK2/STAT3 pathway and promoted HCC cell migration, invasion and proliferation, while repression of miR-103a-3p dramatically upregulated the expression of EVA1A, TP53, BAX and cleaved-caspase-3, inhibited HCC cell migration, invasion and proliferation, and caused mitochondrial dysfunction and apoptosis. Overexpression of EVA1A significantly attenuated the cancer-promoting effects of miR-103a-3p in HCC cells, while knockdown of EVA1A alleviated the mitochondrial dysfunction and apoptosis caused by miR-103a-3p inhibition. Overexpression of EVA1A did not induce significant changes in autophagy levels, nor did it affect G2/M transition or mitosis. Conclusion These findings indicate that the downregulation of the tumor suppressor EVA1A by miR-103a-3p potentially acts as a key mediator in HCC progression, mainly by inhibiting apoptosis and promoting metastasis. The miR-103a/EVA1A/TP53 axis provides a new potential diagnostic and therapeutic target for HCC treatment.

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Section: Discussionsupporting

confidence: 92%

Down-regulation of EVA1A by miR-103a-3p promotes hepatocellular carcinoma cells proliferation and migration

Liao

Gong

et al. 2022

Cell Mol Biol Lett

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“…Cluster B was targeted by miRNAs with established roles in regulating cell-cycle in liver cancer including miR-107, miR-124-3p, and miR-103a-3p. For example, miR-107 is a P53-associated regulator of cell cycle and proliferation, elevated in early-stage liver cancer (58–61); miR-124-3p is a tumor suppressor that regulates proliferation and invasion in liver cancer by inducing G1-phase cell-cycle arrest (62, 63); miR-103a-3p is a promoter of proliferation that is highly dysregulated in liver cancer (64). In cluster C, we found miR-410-3p as a central regulator of the relevant module.…”

Section: Resultsmentioning

confidence: 99%

PanomiR: A systems biology framework for analysis of multi-pathway targeting by miRNAs

Yeganeh

Teo

Karagkouni

et al. 2022

Preprint

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Charting miRNA regulation across multiple pathways is central to characterizing their role in disease. Yet, current methods expose only isolated miRNA-pathway interactions. We have developed a systems biology approach, Pathway networks of miRNA Regulation (PanomiR) that identifies miRNAs that coordinately target groups of pathways. PanomiR captures activity dynamics of pathways, detects dysregulated pathways, groups pathways by their co-expression, and detects miRNAs that specifically target these coordinated groups of dysregulated pathways. We have used PanomiR to explore disease-associated miRNAs and pathways in liver cancer. We show that it recapitulates known and novel liver cancer pathways, determines their up or down regulation, and sensitively captures biologically meaningful signals independent of detectable differential gene expression. PanomiR organizes liver cancer pathways into three broad groups that reflect pathogenic mechanisms of cancer: activation of transcription, cell cycle and proliferation, and dysregulated signalling. Using either experimentally-supported or predicted miRNA-mRNA interactions, PanomiR robustly detects and identifies miRNAs central to liver cancer, unbiased by the number of their gene targets-making it possible to place these cancer miRNAs using PanomiR into the context of co-activated pathways that they regulate. PanomiR is a sensitive, unbiased framework for detection of disease-specific multi-pathway programs under miRNA regulation. PanomiR is accessible as an open-source R/Bioconductor package: <https://bioconductor.org/packages/PanomiR>.

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“…Tumor cells are generally involved in aerobic glycolysis, which leads to a higher demand for glucose in the tumor environment ( 19 , 20 ). When tumor cells were cultured in high-glucose DMEM, in addition to sufficient glucose for biosynthesis, excessive glucose may affect the effect of Con A on tumor cells due to the high affinity of Con A for glucose.…”

Section: Discussionmentioning

confidence: 99%

Concanavalin A inhibits human liver cancer cell migration by regulating F‑actin redistribution and assembly via MAPK signaling pathway

et al. 2022

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Concanavalin A (Con A), the first and most typical representative of the legume lectin family, has a potent anti-liver cancer effect by inducing cell apoptosis and autophagy. However, its function in human liver cancer cell migration remains unclear. The present study investigated the effect of Con A on the viability and migration of human liver cancer cells with different metastatic abilities. It was found that Con A could reduce the viability of human liver cancer cells (HCCLM3, MHCC97L and HepG2) and human hepatocytes (MIHA). In addition, Con A could inhibit human liver cancer cell migration specifically without affecting hepatocytes. Sugar inhibition assay showed that glucose-related sugar binding sites played an important role in the inhibition of Con A on human liver cancer cell migration. In addition, Con A could affect HCCLM3 migration by activating ERK1/2, JNK1/2/3 and p38 signaling in the MAPK pathway. Moreover, Con A could regulate fibrous actin (F-actin) redistribution and assembly via the MAPK signaling pathway. However, Con A had no significant effect on the activation of matrix metalloproteinase (MMP)-2 and MMP-9 in HCCLM3 cells. In conclusion, Con A may bind to glucose-related receptor protein, activating ERK1/2, JNK1/2/3 and p38 signaling in the MAPK pathway, further contracting cells and reducing the content of F-actin of single cells to inhibit HCCLM3 cell migration. These results would deepen the links between human liver cancer cell migration and related glycoproteins or signaling molecules, and may provide a new perspective for Con A as a potential anticancer agent.

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MiR-103a promotes tumour growth and influences glucose metabolism in hepatocellular carcinoma

Cited by 18 publications

References 44 publications

Down-regulation of EVA1A by miR-103a-3p promotes hepatocellular carcinoma cells proliferation and migration

Down-regulation of EVA1A by miR-103a-3p promotes hepatocellular carcinoma cells proliferation and migration

PanomiR: A systems biology framework for analysis of multi-pathway targeting by miRNAs

Concanavalin A inhibits human liver cancer cell migration by regulating F‑actin redistribution and assembly via MAPK signaling pathway

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