Abstract
BackgroundIncreasing evidence suggested that microRNA and kinesin superfamily proteins play an essential role in ovarian cancer. The association between KIF4A and ovarian cancer (OC) was investigated in this study.MethodsWe performed bioinformatics analysis in the GEO database to screen out the differentially expressed miRNAs (DEmiRNAs) associated with ovarian cancer prognosis. Upstream targeting prediction for KIF4A was acquired by using the mirDIP database. The potential regulatory factor miR-29c-3p for KIF4A was obtained from the intersection of the above all miRNAs. The prognosis of KIF4A and target-miRNA in OC was obtained in the subsequent analysis. qRT-PCR and Western blot detected KIF4A expression level in IOSE80 (human normal ovarian epithelial cell line). In the meantime, the gene expression level was detected in A2780, HO-8910PM, COC1, and SKOV3 cell lines (human ovarian carcinoma cell line). MTT and colony formation assays were used to detect cell proliferation of SKOV3 cell line. The following assays detected cell migration through the use of transwell and wound heal assays. Targeted binding relationship between KIF4A and miRNA was detected by using the dual-luciferase reporter assay.ResultsBoth high expression of KIF4A and lower expression of miR-29c-3p could be used as biomarkers indicating poor prognosis in OC patients. Cellular function tests confirmed that when KIF4A was silenced, it inhibited the proliferation and migration of OC cells. In addition, 3′-UTR of KIF4A had a direct binding site with miR-29c-3p, which indicated that the expression of KIF4A could be regulated by miR-29c-3p. In subsequent assays, the proliferation and migration of OC cells were inhibited by the overexpression of miR-29c-3p. At the same time, rescue experiments also confirmed that the promotion of KIF4A could be reversed by miR-29c-3p.ConclusionIn a word, our data revealed a new mechanism for the role of KIF4A in the occurrence and development of OC.
Highlights
Ovarian cancer (OC) has the lowest 5-year survival rate in female cancers because most patients are asymptomatic at an early stage and are already advanced when diagnosed
The results showed that cancer cell lines A2780 (5.532 ± 0.263), SKOV3 (6.565 ± 0.224), HO-8910PM (4.868 ± 0.311), and COC1 (5.486 ± 0.458) express higher Kinesin family member 4A (KIF4A) compared with IOSE80 (P < 0.01), as shown in Fig. 1a and b
Our data have shown that KIF4A was significantly associated with prognosis and act as an oncogene in ovarian cancer (OC)
Summary
Ovarian cancer (OC) has the lowest 5-year survival rate in female cancers because most patients are asymptomatic at an early stage and are already advanced when diagnosed. Diagnosis of ovarian cancer through relevant basic research will maximize fertility preservation. This will significantly reduce the impact on sexual function, mental health, quality of life, and other aspects [1]. Taken together with current studies, more than 650 molecular motor members have been identified, collectively known as kinesin superfamily proteins (KIFs). Such proteins are critical players in the transport of intracellular vesicle and organelle transport along microtubules and cell division [2]. Increasing evidence suggested that microRNA and kinesin superfamily proteins play an essential role in ovarian cancer. The association between KIF4A and ovarian cancer (OC) was investigated in this study
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