miR-663b promotes tumor cell proliferation, migration and invasion in nasopharyngeal carcinoma through targeting TUSC2

Abstract

The authors' previous study revealed that the serum levels of microRNA (miR)-663b are significantly increased in patients with nasopharyngeal carcinoma (NPC), and are associated with NPC progression and poor prognosis. However, the molecular mechanism of underlying NPC growth and metastasis remains unclear. In the present study, quantitative polymerase chain reaction and western blot analyses were performed to examine changes to mRNA and protein expression, respectively. MTT, wound healing and Transwell assays were used to examine cell proliferation, migration and invasion, respectively. Luciferase reporter gene assays were performed to identify target genes of miR-663b. It was demonstrated that miR-663b was significantly upregulated in NPC tissue compared with non-tumor nasopharyngeal epithelial tissue samples. Furthermore, miR-663b expression gradually increased with advancing stages of NPC, with the highest expression being observed in the latest stage IV. The increased expression of miR-663b was associated with advanced clinical stage and lymph node metastasis. In addition, miR-663b expression was increased in NPC cell lines compared with normal nasopharyngeal epithelial NP69 cells. Knockdown of miR-663b resulted in a significant reduction in the proliferation, migration and invasion of NPC CNE1 cells. Tumor suppressor candidate 2 (TUSC2) was identified as a novel target gene of miR-663b. It was further demonstrated that TUSC2 was significantly downregulated in NPC tissue samples and cell lines. miR-663b negatively regulated the expression of TUSC2 at the post-transcriptional level in CNE1 cells. Additionally, inhibition of TUSC2 expression attenuated the suppressive effects of miR-663b downregulation on the proliferation, migration and invasion of CNE1 cells. To the best of our knowledge, this is the first study to demonstrate that miR-663b, which is upregulated in NPC, promotes the proliferation, migration and invasion of NPC cells, partially through the inhibition of TUSC2 expression. Therefore, it is suggested that miR-663b is a promising therapeutic target for the treatment of patients with NPC.

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.…”

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

“…Here, we found that exosomal miR‐663b promoted cell proliferation and the EMT in BC cells, implying it functioned as tumor promoter in BC. Interestingly, miR‐663 are also involved in cancer process with pro‐ or anti‐tumor functions (Zang et al, ; Liang et al, ). Whether there is a relationship between miR‐663 and miR‐663b is worth further studies.…”

“…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.…”

The TUSC2 Tumour Suppressor Inhibits the Malignant Phenotype of Human Thyroid Cancer Cells via SMAC/DIABLO Protein

“…The oncogenic activities of miR-93, miR-98 and miR-197 in lung cancer are mediated by the silencing of TUSC2 [33]. In ovarian and nasopharyngeal cancers it has been reported that miRNA-663 promotes cell growth, migration and invasion by inhibiting TUSC2 [34,35].…”