TSPAN31 regulates the proliferation, migration, and apoptosis of gastric cancer cells through the METTL1/CCT2 pathway

Ma, Xiang; Qiu, Shipei; Tang, Xin; Song, Qingyu; Wang, Pengchao; Wang, Jiawei; Xia, Qingcheng; Wang, Zijun; Zhao, Qinghong; Lu, Ming

doi:10.1016/j.tranon.2022.101423

Cited by 11 publications

(10 citation statements)

References 41 publications

(40 reference statements)

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“…Additionally, our studied five METTL proteins are associated with not only hepatocellular carcinoma but also different human cancers. For example, methyltransferase-like 1 (METTL1) is overexpressed in lung cancer, bladder cancer, lung adenocarcinoma, head and neck squamous cell carcinoma, and gastric cancer [78][79][80][81][82]. On the other hand, methyltransferase-like 3 (METTL3) is upregulated in lung adenocarcinoma, breast carcinoma, triple-negative breast cancer, and several other cancers.…”

Section: Discussionmentioning

confidence: 99%

Small Molecule Inhibitors Targeting Methyltransferase-Like (METTL) Proteins Against Hepatocellular Carcinoma: A Comprehensive Drug Repurposing Approach

Morshed¹,

Parvez

Akanda³

et al. 2023

Preprint

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An efficient and durable multi-targeted therapeutic drug against hepatocellular carcinoma (HCC) has recently been a growing concern for tackling the chemoresistance of approved anti-HCC drugs. Recent studies indicated that methyltransferase-like (METTL) proteins including METTL1, METTL3, METTL6, METTL16, and METTL18, have overexpressed and associated with the progression of HCC malignancy, and making them excellent biomarkers. Here, we present a series of bioinformatics study including novel compound repurposing approach, molecular docking, pharmacophore modeling, and molecular dynamic simulation, which revealed two first-in-class highly potent catalytic multi-target inhibitors (ZINC70666503 and ZINC13000658 with 87% and 82% drug scores, respectively) of methyltransferase-like proteins. Comparatively, these two inhibitors showed a notable binding affinity against studied METTL proteins. Furthermore, ADME and toxicity analysis suggested that these two commercially available compounds have good drug-likeliness properties with no potent toxic effects. Of note, the molecular dynamics study supported their conformational stability and high selectivity at the pocket of proteins' adenosine moiety of S-Adenosyl Methionine. However, this comprehensive analysis needs in vivo validation to facilitate multi-targeting therapeutic development against hepatocellular carcinoma.

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Section: Discussionmentioning

confidence: 99%

Small Molecule Inhibitors Targeting Methyltransferase-Like (METTL) Proteins Against Hepatocellular Carcinoma: A Comprehensive Drug Repurposing Approach

Morshed¹,

Parvez

Akanda³

et al. 2023

Preprint

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“…Human TCP1-containing chaperonin containing TCP1 subunit 2 (CCT2) is an isoform of heat shock protein 60 in eukaryotic cells that is involved in the metabolism of many cells and is highly expressed in many malignant tissues, where tumorigenesis, development, and prognosis are closely related ( 7 , 12 , 13 ). In our study, CCT2 was highly expressed in 27 tumors, and this was confirmed by IHC results.…”

Section: Discussionmentioning

confidence: 99%

“…It has also been shown that TSPAN31 is highly expressed in gastric cancer (GC) tissues and that a high expression of TSPAN31 leads to a poor prognosis in GC patients. TSPAN31 regulates GC cell proliferation, migration, and apoptosis, and this regulatory mechanism is achieved by the co-expression of TSPAN31 ( 12 ). These data suggest that the CCT2 subunit is an important component of chaperone protein activity and is required for some tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive prognostic and immunological analysis of CCT2 in pan-cancer

Shi²,

Pan³

et al. 2022

Front. Oncol.

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CCT2 acts as a molecular chaperone protein that assists in the proper folding of proteins, thus ensuring a dynamic balance of cellular homeostasis. Despite increasing evidence supporting the important role of CCT2 in the tumorigenesis of certain cancers, few articles that provide a systematic pan-cancer analysis of CCT2 have been published. Hence, to evaluate the expression status and prognostic significance of CCT2 in pan-cancers, an analysis of the relationship between CCT2 and different tumor immune cell infiltrations was conducted using datasets from the Cancer Genome Atlas, Cancer Cell Lineage Encyclopedia, and so on. In most cancers, CCT2 expression was high and was associated with poor prognosis. Moreover, CCT2 gene expression was negatively correlated with infiltration of most immune cells in 10 cancer types, and CCT2 expression was related to tumor mutation burden and microsatellite instability. The role that CCT2 plays in tumorigenesis and tumor immunity suggests that it can serve as a prognostic marker in many cancers.

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“…Yan Xu et al found the upregulation of PA2G4 is an unfavorable indicator in the progression of nasopharyngeal cancer 57 . TSPAN31 mediates the proliferation and apoptosis of gastric cancer cells by regulating the CCT2 signaling pathway 58 . CDKN1A has an important role in the response to the cisplatinlJpemetrexed combination in nonlJsmall cell lung cancer cells, which may be used as a predictive marker 59 .…”

Section: Discussionmentioning

confidence: 99%

Transcriptional landscapes and signaling pathways of chloroquine-treated Esophageal squamous cell carcinoma

Wang

Qian

2022

Preprint

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Esophageal squamous cell carcinoma (ESCC) is one of the human malignancies worldwide, but the mechanism of ESCC development is still unclear. Chloroquine has the anti-tumor function by the inhibition of autophagy and thereby contributing to apoptosis. In our study, we analyzed the RNA-seq data of Chloroquine-treated ESCC cells and identified the transcriptional landscapes. We then used the gene enrichment methods such as KEGG and GO to further analyze the potential signaling pathways. In addition, we constructed the PPI network and Reactome map to further identified the biological processes. We identified the top two signaling pathways that were involved in the chloroquine-treated ESCC: Cell cycle and Glycerophospholipid metabolism. We identified the top ten interactive genes including ATM, CCNB1, FN1, CCT6A, VEGFA, PA2G4, CCT2, CDKN1A, BRIX1, and CDC20. Our study may provide new insights into the mechanisms for the Chloroquine-treated ESCC cells.

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TSPAN31 regulates the proliferation, migration, and apoptosis of gastric cancer cells through the METTL1/CCT2 pathway

Cited by 11 publications

References 41 publications

Small Molecule Inhibitors Targeting Methyltransferase-Like (METTL) Proteins Against Hepatocellular Carcinoma: A Comprehensive Drug Repurposing Approach

Small Molecule Inhibitors Targeting Methyltransferase-Like (METTL) Proteins Against Hepatocellular Carcinoma: A Comprehensive Drug Repurposing Approach

Comprehensive prognostic and immunological analysis of CCT2 in pan-cancer

Transcriptional landscapes and signaling pathways of chloroquine-treated Esophageal squamous cell carcinoma

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