RRC ID 63259
Author Suzuki S, Yuan H, Hirata-Tsuchiya S, Yoshida K, Sato A, Nemoto E, Shiba H, Yamada S.
Title DMP-1 promoter-associated antisense strand non-coding RNA, panRNA-DMP-1, physically associates with EGFR to repress EGF-induced squamous cell carcinoma migration.
Journal Mol Cell Biochem
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.
Volume 476(4)
Pages 1673-1690
Published 2021-4-1
DOI 10.1007/s11010-020-04046-5
PII 10.1007/s11010-020-04046-5
PMID 33420898
MeSH Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / metabolism* Carcinoma, Squamous Cell / pathology Cell Line, Tumor Cell Movement* Epidermal Growth Factor / genetics Epidermal Growth Factor / metabolism* ErbB Receptors / biosynthesis ErbB Receptors / genetics Extracellular Matrix Proteins / genetics Extracellular Matrix Proteins / metabolism* Gene Expression Regulation, Neoplastic Humans Neoplasm Proteins / genetics Neoplasm Proteins / metabolism* Phosphoproteins / genetics Phosphoproteins / metabolism* RNA, Antisense / genetics RNA, Antisense / metabolism* RNA, Neoplasm / genetics RNA, Neoplasm / metabolism*
IF 2.795
Human and Animal Cells HuO-3N1(RCB2104) HuO 9N2 (O9N2)(RCB2532) HOS(RCB0992) Saos-2(RCB0428) MG-63(RCB1890)