MiR-15b is a key regulator of proliferation and apoptosis of chondrocytes from patients with condylar hyperplasia by targeting IGF1, IGF1R and BCL2

Abstract

Keywords:MiR-15b Condylar hyperplasia IGF1 IGF1R BCL2 s u m m a r yObjective: This study aimed to explore potential microRNAs (miRNAs), which participate in the pathological process of condylar hyperplasia (CH) through targeting specific proliferation-and apoptosisrelated genes of chondrocytes. Methods: Insulin-like growth factor 1 (IGF1), IGF1 receptor (IGF1R) and B-cell CLL/lymphoma 2 (BCL2) in CH cartilage were detected by real-time polymerase chain reaction (PCR), Western blot, immunohistochemistry and immunofluorescence. MiRanda and TargetScanS algorithms were used to predict certain miRNAs in CH chondrocytes concurrently modulating the above three genes. MiR-15b was screened and identified using real-time PCR. After transfection of miR-15b mimics or inhibitor into CH chondrocytes, expression of the above three genes was detected by real-time PCR and western blot, meanwhile, cell proliferation and apoptosis was examined by CCK8, cell cycle assays, flow cytometry and Hoechst staining. Dual luciferase activity was performed to identify the direct regulation of miR-15b on IGF1, IGF1R and BCL2. Results: Expression of IGF1, IGF1R and BCL2 increased in CH cartilage. Seven microRNAs concurrently correlated with IGF1, IGF1R and BCL2. Among them, only miR-15b significantly changed in CH chondrocytes. Overexpression of miR-15b in CH chondrocytes suppressed the expression of IGF1, IGF1R and BCL2, while it increased when miR-15b was knockdown. Furthermore, miR-15b suppressed their expression by directly binding to its 3 0 -UTR in these cells. Besides, miR-15b hampered chondrocytes proliferation through targeting IGF1 and IGF1R and accelerated chondrocytes apoptosis through targeting BCL2. Conclusion: Suppressed miR-15b contributed to enhanced proliferation capacity and weakened apoptosis of chondrocytes through augmentation of IGF1, IGF1R and BCL2, thereby resulting in development of CH.

Long noncoding RNA LINC00662‐miR‐15b‐5p mediated GPR120 dysregulation contributes to osteoarthritis

“…13 Importantly, a recent study shows that miR-15b is a key regulator of proliferation and apoptosis of chondrocytes from patients with condylar hyperplasia by targeting insulin-like growth factor 1 (IGF1), IGF1 receptor (IGF1R) and B-cell CLL/lymphoma 2 (BCL2). 14 Importantly, the present study shows that LINC00662 was decreased in joint tissue of OA, the sponging effect on miR-15b-5p was increased. Then the inhibitory effect of miR-15b-5p on GPR120 was increased, leading to decreased GPR120 and OA.…”

“…Studies show that miR‐15b‐5p exhibits dual roles by accelerating or blocking tumor progression . Importantly, a recent study shows that miR‐15b is a key regulator of proliferation and apoptosis of chondrocytes from patients with condylar hyperplasia by targeting insulin‐like growth factor 1 (IGF1), IGF1 receptor (IGF1R) and B‐cell CLL/lymphoma 2 (BCL2) …”

“…Consistent with these findings, the present study shows that LINC00662 was involved in the development of OA by miR‐15b‐5p. Indeed, it has been reported that miR‐15b‐5p is a key regulator of proliferation and apoptosis of chondrocytes from patients with condylar hyperplasia by targeting IGF1, IGF1R and Bcl2 . Another study shows that MiR‐15a‐5p regulates viability and matrix degradation of human osteoarthritis chondrocytes via targeting vascular endothelial growth factor A (VEGFA) …”

miR-142-5p as a CXCR4-Targeted MicroRNA Attenuates SDF-1-Induced Chondrocyte Apoptosis and Cartilage Degradation via Inactivating MAPK Signaling Pathway

“…For instance, ectopic expression of miR-204 triggers spontaneous cartilage loss and OA development, whereas miR-204 inhibition results in concomitant recovery of prostaglandins synthesis and suppression of inflammatory senescence-associated secretory phenotype (SASP) factors in experimental OA [16]. It has been demonstrated that miR-15b regulates chondrocytes proliferation and apoptosis by targeting IGF1, IGF1R, and BCL2 from patients with condylar hyperplasia [17] and knockdown of microRNA-203 alleviates LPS-induced injury by targeting MCL-1 in C28/I2 chondrocytes [18]. Recent in vitro studies have revealed that miR-449a inhibition promotes cartilage regeneration and prevents progression of osteoarthritis [19].…”

miR‐15b enhances the proliferation and migration of lung adenocarcinoma by targeting BCL2

“…In several studies, BCL2 has been reported to act as a target gene of multiple miRNAs, including miR‐153, miR‐136 and miR‐365 . BCL2 has also been elucidated to be a target gene of miR‐15b in condylar hyperplasia and liver cancer . miR‐15b has been shown to play a role in the development of multidrug resistance in gastric cancer cells, at least in part by modulation of apoptosis via targeting BCL2 .…”