Emerging Insights into Keratin 16 Expression during Metastatic Progression of Breast Cancer

Elazezy, Maha; Schwentesius, Sandra; Stegat, Luisa; Wikman, Harriet; Werner, Stefan; Mansour, Waël; Failla, Antonio Virgilio; Peine, Sven; Müller, Volkmar; Thiery, Jean Paul; Warkiani, Majid Ebrahimi; Pantel, Klaus; Joosse, Simon A.

doi:10.3390/cancers13153869

Cited by 19 publications

(9 citation statements)

References 39 publications

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“…Keratins have been revealed to play a vital role in the tumorigenesis of numerous cancer types [38][39][40]. In HNSC, highly keratinized squamous cell carcinoma exhibits an improved response to treatment and prognosis compared with weakly keratinized cancer [41].…”

Section: Discussionmentioning

confidence: 99%

The Long Noncoding Transcript HNSCAT1 Activates KRT80 and Triggers Therapeutic Efficacy in Head and Neck Squamous Cell Carcinoma

Zhao

Huang

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Head and neck squamous carcinoma (HNSC) is the most prevalent malignancy of the head and neck regions. Long noncoding RNAs (lncRNAs) are vital in tumorigenesis regulation. However, the role of lncRNAs in HNSC requires further exploration. Herein, through bioinformatic assays using The Cancer Genome Atlas (TCGA) datasets, rapid amplification of cDNA ends (RACE) assays, and RNA-FISH, we revealed that a novel cytoplasmic transcript, HNSC-associated transcript 1 (HNSCAT1, previously recognized as linc01269), was downregulated in tumor samples and advanced tumor stages and was also associated with favorable outcomes in HNSC. Overexpression of HNSCAT1 triggered treatment efficacy in HNSCs both in vivo and in vitro. More importantly, through high-throughput transcriptome analysis (RNA-seq, in NODE database, OEZ007550), we identified KRT80, a tumor suppressor in HNSC, as the target of HNSCAT1. KRT80 expression was modulated by lncRNA HNSCAT1 and presented a positive correlation in tumor samples ( R = 0.52 , p < 0.001 ). Intriguingly, we identified that miR-1245 simultaneously interacts with KRT80 and HNSCAT1, which bridges the regulatory function between KRT80 and HNSCAT1. Conclusively, our study demonstrated that lncRNA HNSCAT1 functions as a necessary tumor inhibitor in HNSC, which provides a novel mechanism of lncRNA function and provides alternative targets for the diagnosis and treatment of HNSC.

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Section: Discussionmentioning

confidence: 99%

The Long Noncoding Transcript HNSCAT1 Activates KRT80 and Triggers Therapeutic Efficacy in Head and Neck Squamous Cell Carcinoma

Zhao

Huang

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…KRT 6A, 16 and 17 were upregulated only in MFUM-BrTNBC-1 compared to MCF-7. Upregulated KRT 6A, 16 and 17 have been associated with EMT in cancer cells [ 60 , 61 , 62 ].…”

Section: Resultsmentioning

confidence: 99%

MFUM-BrTNBC-1, a Newly Established Patient-Derived Triple-Negative Breast Cancer Cell Line: Molecular Characterisation, Genetic Stability, and Comprehensive Comparison with Commercial Breast Cancer Cell Lines

Skok

Gradišnik

Čelešnik

et al. 2021

Cells

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Triple-negative breast cancer (TNBC) is a breast cancer (BC) subtype that accounts for approximately 15–20% of all BC cases. Cancer cell lines (CLs) provide an efficient way to model the disease. We have recently isolated a patient-derived triple-negative BC CL MFUM-BrTNBC-1 and performed a detailed morphological and molecular characterisation and a comprehensive comparison with three commercial BC CLs (MCF-7, MDA-MB-231, MDA-MB-453). Light and fluorescence microscopy were used for morphological studies; immunocytochemical staining for hormone receptor, p53 and Ki67 status; RNA sequencing, qRT-PCR and STR analysis for molecular characterisation; and biomedical image analysis for comparative phenotypical analysis. The patient tissue-derived MFUM-BrTNBC-1 maintained the primary triple-negative receptor status. STR analysis showed a stable and unique STR profile up to the 6th passage. MFUM-BrTNBC-1 expressed EMT transition markers and displayed changes in several cancer-related pathways (MAPK, Wnt and PI3K signalling; nucleotide excision repair; and SWI/SNF chromatin remodelling). Morphologically, MFUM-BrTNBC-1 differed from the commercial TNBC CL MDA-MB-231. The advantages of MFUM-BrTNBC-1 are its isolation from a primary tumour, rather than a metastatic site; good growth characteristics; phenotype identical to primary tissue; complete records of origin; a unique identifier; complete, unique STR profile; quantifiable morphological properties; and genetic stability up to (at least) the 6th passage.

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“…Many keratin genes have been found to affect the occurrence and treatment of breast cancer. Overexpression of KRT16 enhances cell motility and promotes breast cancer metastasis (Elazezy et al, 2021). KRT19 regulates cell proliferation and can predict the effect of CDK inhibitor treatment (Sharma et al, 2019).…”

Section: Frontiers In Geneticsmentioning

confidence: 99%

Genetic instability-related lncRNAs predict prognosis and influence the immune microenvironment in breast cancer

Wang²,

Liu³

et al. 2022

Front. Genet.

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Genome instability is a hallmark of cancer, and the function of lncRNAs in regulating genomic stability has been gradually characterized. However, the prognostic value of lncRNAs related to genetic instability has not been found in breast cancer. Here we constructed a genetic instability-related lncRNA model including U62317.4, SEMA3B-AS1, MAPT-AS1, AC115837.2, LINC01269, AL645608.7, and GACAT2. This model can evaluate the risk and predict the survival outcomes of patients. Further analysis showed that the differentially expressed genes between the high- and low-risk groups were enriched in immunity and cornified envelope formation pathways. In addition, M2 macrophages infiltrated more obviously in the high-risk group. In summary, lncRNAs related to genetic instability may influence the development of breast cancer through immune infiltration and keratinization. This study provides a wider insight into breast cancer development and treatment.

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Emerging Insights into Keratin 16 Expression during Metastatic Progression of Breast Cancer

Cited by 19 publications

References 39 publications

The Long Noncoding Transcript HNSCAT1 Activates KRT80 and Triggers Therapeutic Efficacy in Head and Neck Squamous Cell Carcinoma

The Long Noncoding Transcript HNSCAT1 Activates KRT80 and Triggers Therapeutic Efficacy in Head and Neck Squamous Cell Carcinoma

MFUM-BrTNBC-1, a Newly Established Patient-Derived Triple-Negative Breast Cancer Cell Line: Molecular Characterisation, Genetic Stability, and Comprehensive Comparison with Commercial Breast Cancer Cell Lines

Genetic instability-related lncRNAs predict prognosis and influence the immune microenvironment in breast cancer

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