1. DMP-1 promoter-associated antisense strand non-coding RNA, panRNA-DMP-1, physically associates with EGFR to repress EGF-induced squamous cell carcinoma migration
- Author
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Hideki Shiba, Eiji Nemoto, Akiko Sato, Shigeki Suzuki, Hang Yuan, Kazuma Yoshida, Satoru Yamada, and Shizu Hirata-Tsuchiya
- Subjects
0301 basic medicine ,Small interfering RNA ,Clinical Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Cell Line, Tumor ,medicine ,Humans ,RNA, Antisense ,RNA, Neoplasm ,STAT3 ,Molecular Biology ,Extracellular Matrix Proteins ,Epidermal Growth Factor ,biology ,Chemistry ,RNA ,Cancer ,Cell migration ,Cell Biology ,General Medicine ,Phosphoproteins ,Non-coding RNA ,medicine.disease ,Neoplasm Proteins ,ErbB Receptors ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer cell ,Carcinoma, Squamous Cell ,Cancer research ,biology.protein ,Nuclear localization sequence - Abstract
Accumulating evidence suggests that specific non-coding RNAs exist in many types of malignant tissues, and are involved in cancer invasion and metastasis. However, little is known about the precise roles of non-coding RNAs in squamous cell carcinoma (SQCC) invasion and migration. Recently, the dentin matrix protein-1 (DMP-1) gene locus was identified as a transcriptionally active site in squamous cell carcinoma (SQCC) tissue and cells. However, it is unclear whether RNA associated with cell migration exist at the DMP-1 gene locus in SQCC cells. We identified a novel promoter-associated non-coding RNA in the antisense strand of DMP-1 gene locus, promoter-associated non-coding RNA (panRNA)-DMP-1, by the RACE method in SQCC cells and tissues, and characterized the functions of panRNA-DMP-1 in EGF-driven SQCC cell migration. The inhibition of endogenous panRNA-DMP-1 expression by specific siRNAs and exogenous over-expression of panRNA-DMP-1 resulted in increased and suppressed cellular migration toward EGF in SQCC cells, respectively, and nuclear expression of panRNA-DMP-1 was induced by EGF stimulation. Mechanistically, suppression of panRNA-DMP-1 expression increased EGFR nuclear localization upon EGF treatment and nuclear panRNA-DMP-1 physically interacted with EGFR, which was confirmed by RNA immunoprecipitation assay using a bacteriophage-delivered PP7 RNA labeling system. Furthermore, co-immunoprecipitation assay revealed that suppression of panRNA-DMP-1 stabilized EGFR interaction with STAT3, a known co-transcription factors of EGFR, to induce migratory properties in many cancer cells. Based on these findings, panRNA-DMP-1 is an EGFR-associating RNA that inhibits the EGF-induced migratory properties of SQCC possibly by regulating EGFR nuclear localization and EGFR binding to STAT3.
- Published
- 2021
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