دورية أكاديمية
Head and neck squamous cancer progression is marked by CLIC4 attenuation in tumor epithelium and reciprocal stromal upregulation of miR-142-3p, a novel post-transcriptional regulator of CLIC4 .
| العنوان: | Head and neck squamous cancer progression is marked by CLIC4 attenuation in tumor epithelium and reciprocal stromal upregulation of miR-142-3p, a novel post-transcriptional regulator of CLIC4 . |
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| المؤلفون: | Carofino BL; Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Dinshaw KM; Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.; Department of Molecular and Cellular Biology, University of California, Berkeley, Berkeley, CA, USA., Ho PY; Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.; Department of Pediatrics, Division of Stem Cell Transplantation and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA., Cataisson C; Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Michalowski AM; Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Ryscavage A; Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Alkhas A; Oncology-Gynecology, Park Ridge, IL, USA., Wong NW; CCR Collaborative Bioinformatics Resource (CCBR), Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.; Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Koparde V; CCR Collaborative Bioinformatics Resource (CCBR), Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.; Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Yuspa SH; Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. |
| المصدر: | Oncotarget [Oncotarget] 2019 Dec 31; Vol. 10 (68), pp. 7251-7275. Date of Electronic Publication: 2019 Dec 31 (Print Publication: 2019). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Impact Journals Country of Publication: United States NLM ID: 101532965 Publication Model: eCollection Cited Medium: Internet ISSN: 1949-2553 (Electronic) Linking ISSN: 19492553 NLM ISO Abbreviation: Oncotarget Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Albany, N.Y. : Impact Journals |
| مستخلص: | Chloride intracellular channel 4 (CLIC4) is a tumor suppressor implicated in processes including growth arrest, differentiation, and apoptosis. CLIC4 protein expression is diminished in the tumor parenchyma during progression in squamous cell carcinoma (SCC) and other neoplasms, but the underlying mechanisms have not been identified. Data from The Cancer Genome Atlas suggest this is not driven by genomic alterations. However, screening and functional assays identified miR-142-3p as a regulator of CLIC4 . CLIC4 and miR-142-3p expression are inversely correlated in head and neck (HN) SCC and cervical SCC, particularly in advanced stage cancers. In situ localization revealed that stromal immune cells, not tumor cells, are the predominant source of miR-142-3p in HNSCC. Furthermore, HNSCC single-cell expression data demonstrated that CLIC4 is lower in tumor epithelial cells than in stromal fibroblasts and endothelial cells. Tumor-specific downregulation of CLIC4 was confirmed in an SCC xenograft model concurrent with immune cell infiltration and miR-142-3p upregulation. These findings provide the first evidence of CLIC4 regulation by miRNA. Furthermore, the distinct localization of CLIC4 and miR-142-3p within the HNSCC tumor milieu highlight the limitations of bulk tumor analysis and provide critical considerations for both future mechanistic studies and use of miR-142-3p as a HNSCC biomarker. Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest. |
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| معلومات مُعتمدة: | ZIA BC005445 United States ImNIH Intramural NIH HHS |
| فهرسة مساهمة: | Keywords: immune infiltration; in situ hybridization; miRNA; single-cell RNA-sequencing; stroma |
| تواريخ الأحداث: | Date Created: 20200111 Latest Revision: 20240422 |
| رمز التحديث: | 20240422 |
| مُعرف محوري في PubMed: | PMC6944452 |
| DOI: | 10.18632/oncotarget.27387 |
| PMID: | 31921386 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1949-2553 |
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| DOI: | 10.18632/oncotarget.27387 |