MicroRNA-21-5p are involved in apoptosis and invasion of fibroblast-like synoviocytes through PTEN/PI3K/AKT signal

Abstract

The function of microRNA-21-5p (miR-21) in fibroblast-like synoviocytes in RA was still unclear. In our study, we used tumor necrosis factor alpha (TNFa) (10 ng/ml) to mimic RA-FLSs and we found that normal FLS stimulated with TNFa caused the increasing expression of miR-21, a disintegrin and metalloproteinase with thrombospondin motifs 5 and matrix metalloproteinase 3, which were in accord with RA-FLSs changes. Our data showed that miR-21 overexpression significantly increased cell invasion and decreased apoptosis in FLSs. Knockdown of miR-21 in FLSs causes the opposite result. However, miR-21 may not affect the proliferation of FLSs. Meanwhile, we showed that miR-21 activated the PI3K/ AKT signaling pathway to participate in RA by inhibiting PTEN expression. Taken together, our results suggested that miR-21 may play a positive role in RA and may be a promising new therapeutic target for RA. Keywords Fibroblast-like synoviocytes Á MicroRNA-21-5p Á Apoptosis Á Invasion Á PTEN/PI3K/ AKT signal Xin Yan and Yake Liu have contributed equally to this work.

miR‐21‐5p/SMAD7 axis promotes the progress of lung cancer

“…20 In addition, several studies have confirmed that miRNA-21-5p can regulate tumor cell proliferation, migration and sensitivity to chemotherapy by acting on the tumor suppressor genes PTEN, MARCKS, PDCD4, and Cdc25A. [21][22][23][24] In summary, miRNA-21-5p is closely related to the occurrence and development of various tumors, and can be used for tumor diagnosis, treatment and prognosis, and has important clinical significance. However, due to the lack of in-depth understanding of the transcriptional regulation mechanism of miRNA-21-5p target genes, the clinical application of miRNA-21-5p is limited.…”

“…Yan et al reported that miRNA-21-5p overexpression is associated with specific clinical pathological characteristics of breast cancer, advanced tumor stage, lymph node metastasis, and patient survival. 13 Although many studies have reported that the expression level of miRNA-21-5p is significantly increased in tumor cells and has oncogenic activity, because microRNA has several or even dozens of target genes, the mechanism of cell biological behavior changes caused by miRNA- 21 has not yet been fully elucidated. The relationship between miRNA-21-5p expression and lung cancer has not been fully elucidated, and more detailed mechanism studies are needed to elucidate its complex biological role.…”

Knockdown of circular RNA hsa_circ_0003307 inhibits synovial inflammation in ankylosing spondylitis by regulating the PI3K/AKT pathway

“…Terlemez et al, Yan et al and Liu et al proved that miRNAs affects the phenotype of FLS in rheumatism by regulating the expression of PI3K/AKT, thereby affecting the pathogenesis of rheumatism. [24][25][26] Therefore, we speculate that there may be a regulatory relationship between circRNA_0003307 and the PI3K/AKT pathway.…”

Therapeutic effects of bone marrow mesenchymal stem cells‐derived exosomes on osteoarthritis

“…Osteoarthritis (OA) is the most common type of chronic joint disease throughout the world, with the decline in living standards, functional disability and degenerative joint disorder. 1 , 2 Clinically, osteoarthritis (OA) is characterized by degradation of articular cartilage, inflammation of synovial and remodelling of subchondral bone. 3 , 4 OA patients suffer from severe pain, limitation of movement and a high risk of disability.…”