Blockade of miR-663b inhibits cell proliferation and induces apoptosis in osteosarcoma via regulating TP73 expression

Abstract

OBJECTIVE: This study aimed to investigate the exact role of miR-663b in osteosarcoma (OS) progression and further explore the underlying molecular mechanisms. MATERIALS AND METHODS: The miR-663b expression in human OS cell lines was determined by qRT-PCR, and the results suggested that miR-663b was highly expressed in human OS cells. TargetScan was used to predict the potential targets of miR-663b, and the prediction was confi rmed by dual-luciferase reporter assay. To investigate the role of miR-663b in OS, miR-663b was down-regulated in U2OS cells using miR-663b inhibitor. CCK8 and fl ow cytometry were preformed to investigate the proliferation and apoptosis of U2OS cells. Moreover, qRT-PCR and western blot analysis were performed to measure the mRNA and protein expression. RESULTS: We found that miR-663b directly targets TP73 and negatively regulates TP73 expression. MiR-663b inhibitor signifi cantly decreased the proliferation ability of U2OS cells, while the percentage of apoptotic cells was markedly increased. The level of Bcl-2 was notably inhibited by miR-663b inhibitor, while Bax expression was signifi cantly enhanced. Moreover, miR-663b down-regulation promoted p53 and p21 expression in U2OS cells. CONCLUSIONS: MiR-663b down-regulation represses proliferation and induces apoptosis in OS by targeting TP73. Therefore, we provide a potential therapeutic target for OS treatment (Fig. 6, Ref. 27). Text in PDF www.elis.sk.

MicroRNA‑663b enhances migration and invasion by targeting adenomatous polyposis coli 2 in colorectal carcinoma cells

“…Accumulating evidence indicates that the dysregulation of miRNAs is involved in various types of diseases (23,24). The abnormal expression of miR-663b has been observed in a variety of malignancies: Shu et al (25) demonstrated that the knockdown of miR-663b inhibited cell proliferation and promoted apoptosis in osteosarcoma by regulating tumor (26) identified that miR-497 and miR-663b levels in the plasma may be novel biomarkers for bladder cancer; Cai et al (27) suggested that the epigenetic inhibition of miR-663b by HOTAIR promotes cell proliferation in pancreatic cancer by upregulating insulin-like growth factor 2; Wang et al (28) reported that miR-663b promotes cell proliferation and epithelial-to-mesenchymal transition by directly targeting SMAD7 in nasopharyngeal carcinoma; Wang et al (29) demonstrated that pterostilbene dose-dependently inhibited cell proliferation in human endometrial cancer by downregulating miR-663b, and BCL2L14 was verified as a direct target of miR-663b; Liang et al (30) revealed that miR-663b promotes migration and invasion of nasopharyngeal carcinoma cells through downregulating TUSC2; and, using a miRNA microarray analysis, Pellatt et al (15) recently demonstrated that miR-663b is upregulated in CRC tissues compared with normal mucosa. However, the mechanism of action of miR-663b in CRC remains elusive.…”

Targeting Super-Enhancer–Associated Oncogenes in Osteosarcoma with THZ2, a Covalent CDK7 Inhibitor

“…Interestingly, we observed a number of top-ranking super-enhancer-associated genes that have been proven to be associated with osteosarcoma oncogenic transcripts in previous studies, such as MYC (35), PIM1 (36), TCF7L2 (37), and HMOX1 (38). In addition to coding RNAs, these super-enhancers have been reported to drive the expression of long non-coding RNAs such as MALAT1 (39), and microRNAs such as MIR663B (40) and MIR21 (41), which have been reported to contribute to osteosarcoma malignancy. In addition, some lineage-specific transcription factors which regulate skeletal development, such as GLI2 (42), LIF (43), MDM2 (44), RUNX2 (45), and EGFR (46), were found to be associated with super-enhancers ( Fig.…”

Exosomal miR‐663b targets Ets2‐repressor factor to promote proliferation and the epithelial–mesenchymal transition of bladder cancer cells

“…The miR‐663b has been demonstrated to promote cell proliferation, migration, invasion, and EMT in nasopharyngeal carcinoma (Liang et al, ; Wang et al, ). Blockade of miR‐663b inhibited cell proliferation and induced apoptosis in osteosarcoma (Shu et al, ), whereas miR‐663b was shown to exert tumor‐suppressive functions in pancreatic cancer (Cai et al, ). Here, we found that exosomal miR‐663b promoted cell proliferation and the EMT in BC cells, implying it functioned as tumor promoter in BC.…”

“…miR‐663b has been found to be elevated in plasma from patients with BC and was identified as a potential circulating biomarker for clinical detection of BC (Du et al, ). It has been reported that miR‐663b promotes tumor cell proliferation and the epithelial–mesenchymal transition (EMT) in nasopharyngeal carcinoma (Liang et al, ; Wang et al, ) and osteosarcoma (Shu et al, ). However, whether it exists in the exosomes and the functional roles of exosomal miR‐663b in BC processes have not been determined.…”