Abstract
Circular RNAs (circRNAs) have demonstrated critical roles in the development of cancers. This study aimed to explore the function of circular RNA circPRKCI/miR-20a-5p/SOX4 axis in acute lymphoblastic leukemia (ALL). Our data showed that the expression of circPRKCI and SOX4 was enhanced while the expression of miR-20a-5p was reduced in the clinical T-ALL samples. The expression of miR-20a-5p was negatively associated with circPRKCI and SOX4 in the T-ALL patients and the expression of circPRKCI was positive correlated with SOX4 in the T-ALL patients. Functionally, the silencing of circPRKCI suppressed the viability of T-ALL cells. Conversely, the knockdown of circPRKCI promoted the apoptosis of T-ALL cells. The levels of cleaved PARP and cleaved caspase3 were induced by the depletion of circPRKCI in T-ALL cells. Mechanically, the luciferase activity of circPRKCI was significantly decreased in T-ALL cells after the treatment of miR-20a-5p mimic. Meanwhile, the silencing of circPRKCI promoted the expression of miR-20a-5p in T-ALL cells, implying that circPRKCI serves as a competitive endogenous RNAs (ceRNA) of miR-20a-5p. We validated that the treatment of miR-20a-5p mimic inhibited the viability of T-ALL cells. MiR-20a-5p mimic enhanced the apoptosis of T-ALL cells. The expression of cleaved PARP and cleaved caspase3 was increased by miR-20a-5p mimic in the cells. In summarization, we concluded that circular RNA circPRKCI contributed to malignant progression of T-cell acute lymphoblastic leukemia by modulating miR-20a-5p/SOX4 axis. Targeting circPRKCI may serve as a promising therapeutic strategy of T-ALL.
Highlights
Acute lymphoblastic leukemia (ALL) is the most frequently occurred malignancy in children, among which T-cell ALL (T-ALL) accounts for almost 20% of all newly diagnosed ALL cases both in children and adults [1]
The expression levels of circPRKCI are positive correlated with SOX4 and are negative correlated with miR-20a-5p in T-ALL samples
To determine the correlation of circPRKCI, miR-20a5p, and SOX4 in the development of T-ALL, we evaluated the expression levels of circPRKCI, miR-20a5p, and SOX4 in clinical T-ALL samples
Summary
Acute lymphoblastic leukemia (ALL) is the most frequently occurred malignancy in children, among which T-cell ALL (T-ALL) accounts for almost 20% of all newly diagnosed ALL cases both in children and adults [1]. Numerous studies have proposed abnormal levels of circRNAs and their remarkable functions in various diseases, especially in cancers [7]. Silencing of circPRKCI suppressed the growth of esophageal cancer and enhanced sensitivity of cell to radiation through PARP signaling [9]. Studies showed that circRNAs affected gene expression through acting as sponges of microRNAs (miRNAs) [6]. MiRNAs act as tumor suppressors or activators through interacting with the 3’UTR areas of specific mRNAs to suppress gene translation, which causes the dysregulation of cellular process including growth and metastasis of cancer cells [10]. Its role in T-ALL is yet to be defined
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