Knockdown of CCNO decreases the tumorigenicity of gastric cancer by inducing apoptosis

Abstract

PurposeRecently, Cyclin O (CCNO) has been reported to be a novel protein of the cyclin family. However, the clinical significance and functional roles of CCNO in human cancer, including gastric cancer (GC), remain largely unexplored. In this study, we investigated the clinical and functional roles of CCNO in GC.MethodsWe analyzed CCNO expression patterns in GC patients. To investigate the role of CCNO in malignancy of GC, we used lentivirus-delivered short hairpin RNA to knockdown CCNO expression in GC cell lines. Then multiparametric high-content screening and MTT incorporation assay were used to assess the cell proliferation capability. Cell apoptosis was detected by flow cytometry and Caspase 3/7 assays. Furthermore, the effect of CCNO on tumorigenicity of GC was also determined in vivo. Finally, microarray analysis was performed to elucidate the molecular mechanisms by which shCCNO inhibited the malignancy of GC cells.ResultsThe analysis from The Cancer Genome Atlas database revealed elevated CCNO mRNA expression in GC tissue than in the adjacent normal tissue. Immunohistochemical studies also showed that stronger cytoplasmic staining of CCNO was detected in GC tissues. Downregulation of CCNO in GC cells efficiently, through infection with the lentivirus-mediated specific short hairpin RNA, could significantly induce cell apoptosis and inhibit the proliferative properties both in vitro and in vivo. Microarray analysis further revealed 652 upregulated genes and 527 downregulated genes in the shCCNO group compared with control, and indicated that CCNO knockdown could inhibit the malignancy of GC cells through inducing genome-wide gene expression changes.ConclusionOur work is the first to reveal that elevated CCNO expression is closely associated with human GC development and that CCNO knockdown could efficiently inhibit the malignant properties of GC cells by inducing cell apoptosis. Therefore, CCNO could be used as a potential biomarker for prognosis or even as a therapeutic target in human GC.

RACK1 promotes miR-302b/c/d-3p expression and inhibits CCNO expression to induce cell apoptosis in cervical squamous cell carcinoma

“…In the present study, CCNO was identified as the target of miR-302b/c/d-3p. In addition, elevated mRNA expression of CCNO has been reported in GC tissues and depletion of CCNO can significantly induce cancer cell apoptosis both in vitro and in vivo [ 18 ], which is partially consistent with our findings.…”

“…In the present study, CCNO was identified as the target of miR-302b/c/d-3p. In addition, elevated mRNA expression of CCNO has been reported in GC tissues and depletion of CCNO can significantly induce cancer cell apoptosis both in vitro and in vivo [18], which is partially consistent with our findings. Our study also revealed that up-regulated RACK1 inhibited CCNO expression by promoting miR-302b/c/d-3p expression, resulting in accelerated apoptosis in CSCC cells, as evidenced by decreased Bcl-2 and Cyclin D1 expression, and increased cleaved PARP and cleaved caspase 3 expression.…”

“…CCNO has been identified as a novel protein of the cyclin family, and is known to be involved in the regulation of oocyte meiotic progression at different stages [17]. Its down-regulation inhibits the tumorigenicity of GC by enhancing cell apoptosis [18]. These findings led to the hypothesis that RACK1 might participate in the development of CSCC through the regulation of miR-302b/c/d-3p and CCNO.…”

Transcriptional regulation of multiciliated cell differentiation

“…Aberrant expression of key MCC specific genes can also be observed in many cancers and some evidence suggests they may play functional roles [138][139][140]. The aberrant expression or depletion of GEMC1 and MCIDAS in cancer cell lines has been shown to impact DNA replication and could potentially activate transcription factors such as E2F4, p73 and FOXJ1 that have been implicated in cancer development, and could provoke centriole amplification and mitotic defects [26][27][28].…”

Plasma Exosomal miRNA Levels after Radiotherapy Are Associated with Early Progression and Metastasis of Cervical Cancer: A Pilot Study

“…The pelvic RT dose was 45 Gy, delivered in 25 fractions, with a simultaneous integrated boost of 120-130% to regional LN metastases. RT response was evaluated by MRI in the fourth week of pelvic EBRT (36)(37)(38)(39)(40)(41)(42)(43)(44)(45) Gy in 20-25 fractions). A weekly cisplatin regimen (30-70 mg/m 2 ) was administered for six cycles to all patients.…”