Raikundalia Sweta, Sa'Dom Siti Aisyah Faten Mohamed, Few Ling Ling, Too Wei Cun See
School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia.
Oncol Lett. 2021 Mar;21(3):183. doi: 10.3892/ol.2021.12444. Epub 2021 Jan 6.
Choline kinase (ChK) catalyzes the first step in the CDP-choline pathway for the synthesis of phosphatidylcholine. The α isoform of this enzyme is overexpressed in various types of cancer and its inhibition or downregulation has been applied as an anticancer strategy. In spite of increasing attention being paid to ChK expression, as well as its activity and inhibition in cancer, there are only limited studies available on the regulation of ChK, including its regulation by microRNAs (miRNAs/miRs). The dysregulation of gene expression by miRNAs is a common cause for carcinogenesis. In the present study, miR-367-3p was predicted to target the 3'-untranslated region (UTR) of the ChK α () mRNA transcript. The binding of miR-367-3p to the 3'-UTR of was validated by a luciferase assay. The effects of the miR-367-3p mimic on gene and protein expression levels were determined by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. miR-367-3p significantly downregulated the expression of to ~60% of the negative control. Cells transfected with miR-367-3p exhibited higher levels of apoptosis and a lower cell migration compared with the control. To the best of our knowledge, the present study provided the first experimental evidence of the regulation of expression by miR-367-3p. The pro-apoptotic and suppressive effects of miR-367-3p on cell migration were similar to the anticancer effects resulting from the inhibition of ChK enzyme activity or the knockdown of gene expression by small interfering RNA. Therefore, these findings may potentially lead to the use of miR-367-3p in anticancer strategies that target ChK.
胆碱激酶（ChK）催化磷脂酰胆碱合成的CDP-胆碱途径中的第一步。该酶的α亚型在多种癌症中过表达，其抑制或下调已被用作一种抗癌策略。尽管人们越来越关注ChK在癌症中的表达、活性及抑制作用，但关于ChK调控的研究，包括其受微小RNA（miRNA/miR）调控的研究仍然有限。miRNA导致的基因表达失调是致癌的常见原因。在本研究中，预测miR-367-3p靶向ChKα（）mRNA转录本的3'-非翻译区（UTR）。通过荧光素酶测定法验证了miR-367-3p与的3'-UTR的结合。分别通过逆转录-定量聚合酶链反应和蛋白质印迹分析确定了miR-367-3p模拟物对基因和蛋白质表达水平的影响。miR-367-3p显著下调的表达至阴性对照的约60%。与对照相比，转染miR-367-3p的细胞表现出更高的凋亡水平和更低的细胞迁移能力。据我们所知，本研究提供了miR-367-3p调控表达的首个实验证据。miR-367-3p对细胞迁移的促凋亡和抑制作用类似于抑制ChK酶活性或通过小干扰RNA敲低基因表达所产生的抗癌作用。因此，这些发现可能会促使miR-367-3p用于靶向ChK的抗癌策略。
