miR‑539 suppresses the proliferation, migration, invasion and epithelial mesenchymal transition of pancreatic cancer cells through targeting SP1

Abstract

MicroRNA (miR)-539 has inhibitory effects on certain types of cancer, but its role in pancreatic cancer (Pca) remains unclear. The present study investigated the effects of miR-539 on Pca, and aimed to determine possible therapeutic targets for the treatment of Pca. The expression of miR-539 in Pca tissues, paired normal adjacent tissues and Pca cell lines (cAPAN-2, BxPc3, cFPAc1, SW1990 and PANc1), and human non-cancerous pancreatic cells (hTRET-HPNE) was determined and compared. The effects of upregulation and downregulation of miR-539 on proliferation, apoptosis, cell cycle, invasion, migration and epithelial-mesenchymal transition (EMT) of Pca cells were investigated. Additionally, the target gene of miR-539 was predicted and its effects on Pca cells were further investigated. The results revealed low expression of miR-539 in Pca tissues and cell lines. Additionally, increasing miR-539 expression inhibited the proliferation, migration, invasion and EMT of Pca cells and induced apoptosis by blocking G1 phase of the cell cycle, while reducing miR-539 expression had the opposite results. Furthermore, specificity protein 1 (SP1) was found to be the target gene of miR-539. SP1 promoted the proliferation, migration, invasion and EMT transformation of Pca cells, but these effects were reversed by high expression of miR-539. Additionally, miR-539 suppressed the proliferation, metastasis, invasion and EMT transformation of Pca cells through targeting SP1. Therefore, miR-539 overexpression may contribute toward development of novel therapeutic strategies for Pca in the future.

Specificity protein 1‑activated bone marrow stromal cell antigen 2 accelerates pancreatic cancer cell proliferation and migration

“…Targeted inhibition of SP1 by miR-502-5p in gastric cancer cells decreased the levels of cell proliferation, invasion and migration ( 30 ). Moreover, in a previous study, SP1 was found to be targeted by miR-529, thereby suppressing the malignant behaviors and epithelial-to-mesenchymal transition of pancreatic cancer cells ( 31 ). lncRNA-LINC00514 upregulation mediated via SP1 acts as an oncogene in metastatic osteosarcoma by regulating miR-708 expression ( 32 ).…”

PPP3CB inhibits pancreatic cancer progression via promoting translocation of ATOH8 and further transcriptionally regulating Sp1

“…Our previous work has brought to light the constitutive expression of Sp1 in PDAC [30][31][32] . Sp1, known to induce EMT by interacting with transcription factors and suppressors such as Twist or Snail, plays a pivotal role in tumor metastasis 33,34 .…”

miR-539-5p targets BMP2 to regulate Treg activation in B-cell acute lymphoblastic leukemia through TGF-β/Smads/MAPK

“…MiRNA is a class of endogenous non-coding single-stranded small RNA, which is involved in the regulation of post-transcriptional gene expression by specifically binding to the target genes [ 26 , 27 ]. MiR-539 has been confirmed as a suppressor factor in cancers, and plays an inhibitory role in a variety of cancers, including breast cancer [ 28 ], osteosarcoma [ 29 ], and pancreatic cancer [ 30 ]. However, there are no relevant research reports on miRNA-539-5p in B-ALL at present.…”