MicroRNA‑495 targets Notch1 to prohibit cell proliferation and invasion in oral squamous cell carcinoma

Abstract

MicroRNAs (miRNAs) are associated with the initiation and progression of oral squamous cell carcinoma (OSCC) by regulating a variety of cancer-associated behaviors. Fully understanding the regulatory mechanism of miRNAs in the pathogenesis of OSCC may provide novel promising approaches for the identification of prognostic biomarkers and therapeutic targets for this particular malignancy. In the present study, reverse transcription-quantitative polymerase chain reaction analysis was performed to detect miRNA (miR)-495 expression in OSCC tissues and cell lines. The effects of miR-495 on the proliferation and invasion of OSCC cells were determined using Cell Counting Kit-8 and Matrigel invasion assays, respectively. The mechanisms underlying the action of miR-495 in OSCC cells were also investigated. Results from the present study revealed that miR-495 expression was downregulated in OSCC tissues and cell lines compare with in adjacent normal tissues and human oral keratinocytes, respectively. Exogenous expression of miR-495 restricted cell proliferation and invasion of OSCC cells in vitro. Notch1 was identified as a direct functional target of miR-495 in OSCC. Furthermore, Notch1 knockdown exhibited inhibitory effects, similar to those induced by miR-495 overexpression in OSCC cells. Restoration of Notch1 expression rescued the suppressive effects of miR-495 on OSCC cell proliferation and invasion. These findings suggested an important role for miR-495 in the regulation of OSCC cell growth and metastasis, at least partly by directly targeting Notch1. In addition, the findings of the present study revealed the potential of miR-495 as a novel therapeutic target for the treatment of patients with OSCC.

MicroRNA-495 serves as a diagnostic biomarker in patients with sepsis and regulates sepsis-induced inflammation and cardiac dysfunction

“…For example, in endometrial cancer (EC), miR-495 was downregulated in tumor tissues, and overexpression of miR-495 markedly inhibited tumor cell proliferation and promoted cell apoptosis via targeting PIK3R1 [28]. In oral squamous cell carcinoma (OSCC), miR-495 was also reported to play an antitumor effect through regulating OSCC cell growth and metastasis [29]. In healthy cells, miR-495 was also reported to participate in a variety of developmental, apoptotic, immune and inflammatory mechanisms [30].…”

MicroRNA-495 confers inhibitory effects on cancer stem cells in oral squamous cell carcinoma through the HOXC6-mediated TGF-β signaling pathway

“…In the current study, overexpression of miR-495 inhibited the proliferation, migration, and invasion while stimulating the apoptosis of CSCs in OSCC by downregulating its target HOXC6 gene. Similarly, the overexpression of miR-495 inhibits OSCC cell proliferation and invasion through its suppression in Notch1 target gene in vitro [10]. One previous study suggested that 14q32.31 miRNAs, including miR-495, play important roles in the inhibition of cell proliferation, invasion, and migration in metastatic prostate cancer, where miR-495 could decrease cells in proliferative S phase while increase cells in the G1 phase [37].…”

“…A recent study suggests that miR-495 may serve as a tumor suppressor by inhibiting the migration and invasion of gastric cancer cells [9]. In addition, restored miR-495 expression can restrict cell proliferation and invasion in OSCC cells in vitro by repressing its target gene Notch1 [10]. The HOX gene family consists of 39 genes that organize into 4 chromosomal loci, which has been reported to play a significant role in organogenesis via regulation of proliferation, differentiation, survival, migration, and invasion [11].…”

Regulation of Abnormal Expression of hsa_circRNA_0127523 on Proliferation, Migration and Invasion and miR-515-5p Expression in Oral Squamous Cell Carcinoma.

“…Lv et al has found that miR-495 restricts the proliferation and invasion of OSCC cells by directly targeting Notch1. Notch1 knockdown shows an inhibitory effect similar to that induced by miR-495 overexpression in OSCC cells [46]. Cyclin-dependent kinase (CDK) and cyclin-dependent kinase inhibitor (CDKI) can directly control the cell cycle.…”