Mucin 21 is a key molecule involved in the incohesive growth pattern in lung adenocarcinoma

Yoshimoto, Taichiro; Matsubara, Daisuke; Soda, Manabu; Ueno, Toshihide; Amano, Yusuke; Kihara, Atsushi; Sakatani, Takashi; Nakano, Tomoyuki; Shibano, Tomoki; Endo, Shunsuke; Hagiwara, Koichi; Fukayama, Masashi; Denda-Nagai, Kaori; Irimura, Tatsuro; Mano, Hiroyuki; Niki, Toshiro

doi:10.1111/cas.14129

Cited by 23 publications

(24 citation statements)

References 17 publications

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“…However, in addition to roles as epithelial protectants, mucins and related proteins also serve roles in cell signaling with physiological consequences. This is recently shown for MUC21 overexpression as influencing the development of lung adenocarcinoma [ 78 ] and TFF1 influencing epithelial-mesenchymal transition. Together, this may be a contributing factor to the STRING cluster of keratinocyte differentiation factors discussed below, but further study is warranted to determine which cell types are expressing these genes and which cell signaling may be impacted.…”

Section: Discussionmentioning

confidence: 68%

RNA sequencing identifies transcriptional changes in the rabbit larynx in response to low humidity challenge

et al. 2020

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Background Voice disorders are a worldwide problem impacting human health, particularly for occupational voice users. Avoidance of surface dehydration is commonly prescribed as a protective factor against the development of dysphonia. The available literature inconclusively supports this practice and a biological mechanism for how surface dehydration of the laryngeal tissue affects voice has not been described. In this study, we used an in vivo male New Zealand white rabbit model to elucidate biological changes based on gene expression within the vocal folds from surface dehydration. Surface dehydration was induced by exposure to low humidity air (18.6% + 4.3%) for 8 h. Exposure to moderate humidity (43.0% + 4.3%) served as the control condition. Ilumina-based RNA sequencing was performed and used for transcriptome analysis with validation by RT-qPCR. Results There were 103 statistically significant differentially expressed genes identified through Cuffdiff with 61 genes meeting significance by both false discovery rate and fold change. Functional annotation enrichment and predicted protein interaction mapping showed enrichment of various loci, including cellular stress and inflammatory response, ciliary function, and keratinocyte development. Eight genes were selected for RT-qPCR validation. Matrix metalloproteinase 12 (MMP12) and macrophage cationic peptide 1 (MCP1) were significantly upregulated and an epithelial chloride channel protein (ECCP) was significantly downregulated after surface dehydration by RNA-Seq and RT-qPCR. Suprabasin (SPBN) and zinc activated cationic channel (ZACN) were marginally, but non-significantly down- and upregulated as evidenced by RT-qPCR, respectively. Conclusions The data together support the notion that surface dehydration induces physiological changes in the vocal folds and justifies targeted analysis to further explore the underlying biology of compensatory fluid/ion flux and inflammatory mediators in response to airway surface dehydration.

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Section: Discussionmentioning

confidence: 68%

RNA sequencing identifies transcriptional changes in the rabbit larynx in response to low humidity challenge

et al. 2020

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show abstract

“…However, in addition to roles as epithelial protectants, mucins and related proteins also serve roles in cell signaling with physiological consequences. This is recently shown for MUC21 overexpression as in uencing the development of lung adenocarcinoma (89) and TFF1 in uencing epithelial-mesenchymal transition. Together, this may be a contributing factor to the STRING cluster of keratinocyte differentiation factors discussed below, but further study is warranted to determine which cell types are expressing these genes and which cell signaling may be impacted.…”

Section: Discussionmentioning

confidence: 59%

RNA sequencing identifies transcriptional changes in the rabbit larynx in response to low humidity challenge

Bailey

Santos

Nascimento

et al. 2020

Preprint

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Background Voice disorders are a worldwide problem impacting human health, particularly for occupational voice users. Avoidance of surface dehydration is commonly prescribed as a protective factor against the development of dysphonia. The available literature inconclusively supports this practice and a biological mechanism for how surface dehydration of the laryngeal tissue affects voice has not been described. In this study, we used an in vivo male New Zealand white rabbit model to elucidate biological changes based on gene expression within the vocal folds from surface dehydration. Surface dehydration was induced by exposure to low humidity air (18.6% ± 4.3%) for 8 hours. Exposure to moderate humidity (43.0% ± 4.3%) served as the control condition. Ilumina-based RNA sequencing was performed and used for transcriptome analysis with validation by RT-qPCR. Results There were 103 genes identified through Cuffdiff with 64 genes meeting significance by both false discovery rate and fold change. Functional annotation enrichment and predicted protein interaction mapping showed enrichment of various loci, including cellular stress and inflammatory response, ciliary function, and keratinocyte development. Eight genes were selected for RT-qPCR validation. Matrix metalloproteinase 12 (MMP12) and macrophage cationic peptide 1 (MCP1) were significantly upregulated and an epithelial chloride channel protein (ECCP) was significantly downregulated after surface dehydration by RNA-Seq and RT-qPCR. Suprabasin (SPBN) and zinc activated cationic channel (ZACN) were marginally, but non-significantly down- and upregulated by RT-qPCR, respectively. Conclusions The data together support the notion that surface dehydration induces physiological changes in the vocal folds and justifies targeted analysis to further explore the underlying biology of compensatory fluid/ion flux and inflammatory mediators in response to airway surface dehydration.

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“…In recent years, correlation studies showed an association between mucin overexpression and glycosylation with cancer formation, prognosis, and metastasis (Behera et al, 2015). MUC 1, 2, 3, 5AC, 5B, 8, 16, and 21 are related, to a different degree, in breast (Masaki et al, 1999), ovarian (Yin and Lloyd, 2001; Wang and El-Bahrawy, 2015), endometrial tumors (Hebbar et al, 2005), prostate (Xiong et al, 2006), pancreatic (Levi et al, 2004), gastric and cervical (Kaur et al, 2013), colorectal (Chang et al, 1994), renal cell carcinoma (Leroy et al, 2002), pseudoxyoma periotonei (Ciriza et al, 2000), and recently studied lung cancer (Yoshimoto et al, 2019). There are multiple recent reviews about the role on mucins and cancer for further reading (Chugh et al, 2015; Dhanisha et al, 2018; Kasprzak and Adamek, 2019).…”

Section: Mucins Mlms and Diseasesmentioning

confidence: 99%

Mucins and Pathogenic Mucin-Like Molecules Are Immunomodulators During Infection and Targets for Diagnostics and Vaccines

2019

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Mucins and mucin-like molecules are highly O-glycosylated proteins present on the cell surface of mammals and other organisms. These glycoproteins are highly diverse in the apoprotein and glycan cores and play a central role in many biological processes and diseases. Mucins are the most abundant macromolecules in mucus and are responsible for its biochemical and biophysical properties. Mucin-like molecules cover various protozoan parasites, fungi and viruses. In humans, modifications in mucin glycosylation are associated with tumors in epithelial tissue. These modifications allow the distinction between normal and abnormal cell conditions and represent important targets for vaccine development against some cancers. Mucins and mucin-like molecules derived from pathogens are potential diagnostic markers and targets for therapeutic agents. In this review, we summarize the distribution, structure, role as immunomodulators, and the correlation of human mucins with diseases and perform a comparative analysis of mucins with mucin-like molecules present in human pathogens. Furthermore, we review the methods to produce pathogenic and human mucins using chemical synthesis and expression systems. Finally, we present applications of mucin-like molecules in diagnosis and prevention of relevant human diseases.

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Mucin 21 is a key molecule involved in the incohesive growth pattern in lung adenocarcinoma

Cited by 23 publications

References 17 publications

RNA sequencing identifies transcriptional changes in the rabbit larynx in response to low humidity challenge

RNA sequencing identifies transcriptional changes in the rabbit larynx in response to low humidity challenge

RNA sequencing identifies transcriptional changes in the rabbit larynx in response to low humidity challenge

Mucins and Pathogenic Mucin-Like Molecules Are Immunomodulators During Infection and Targets for Diagnostics and Vaccines

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