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
|
Resource |
Human and Animal Cells |
HuO-3N1(RCB2104)
HuO 9N2 (O9N2)(RCB2532)
HOS(RCB0992)
Saos-2(RCB0428)
MG-63(RCB1890) |