The Circular RNA circXPO1 Promotes Tumor Growth via Sponging MicroRNA-23a in Prostate Carcinoma

Zou²,

et al. 2023

Hereditas

Background Circular RNAs (circRNAs) are abnormally expressed in breast cancer (BC). However, the biological function and mechanism of circHMCU still need to be further explored. Methods The expression levels of circHMCU, miR-4458 and phosphoglycerate kinase 1 (PGK1) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The glucose uptake, lactate production and ATP level were assayed by related commercial kits. Cell Counting Kit-8 (CCK8), 5’-ethynyl-2’-deoxyuridine (EdU) and flow cytometry assays were used to test cell proliferation and apoptosis, respectively. The migratory and invasive abilities were detected by transwell and wound-healing assays. The relationships among circHMCU, miR-4458 and PGK1 were verified by dual-luciferase reporter assay. The function of circHMCU in tumor growth was evaluated by animal studies. Results CircHMCU was upregulated in BC tissues and cell lines, whereas miR-4458 was downregulated. For biological experiments, circHMCU knockdown inhibited cell proliferation, migration, glycolysis, while promoted cell apoptosis. CircHMCU bound miR-4458, and miR-4458 targeted PGK1. MiR-4458 inhibition reversed circHMCM knockdown-mediated effects on BC cell malignant behaviors. MiR-4458 overexpression suppressed cell glycolysis, proliferation, and metastasis and promoted apoptosis in BC cells through PGK1 upregulation. Additionally, circHMCU suppressed tumor growth in vivo. Conclusion CircHMCU acted as an oncogenic factor by regulating the miR-4458/PGK1 axis in BC.

Section: Discussionmentioning

confidence: 99%

Circular RNA circHMCU promotes breast tumorigenesis through miR-4458/PGK1 regulatory cascade

Zou²,

et al. 2023

Hereditas

“…CircXPO1 could promote the oncogenesis of prostate cancer by targeting miR-23a (Chen et al, 2021 ). CircXPO1 could regulate multiple miRNAs and, enhance the proliferation capacity and migration of osteosarcoma cells via up-regulating XPO1 (Jiang et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Circular RNA circXPO1 Promotes Multiple Myeloma Progression by Regulating miR-495-3p/DNA Damage-Induced Transcription 4 Axis

Li,

Liu,

Miao

et al. 2024

DNA and Cell Biology

Multiple myeloma (MM) is a hematologic malignancy that results from uncontrolled plasma cell proliferation. Circular RNAs are versatile regulators that influence cancer aggression. The pathogenic mechanism of circXPO1 in MM is still unknown. In this study, the expression of circXPO1, miR-495-3p, and DNA damage-induced transcription 4 ( DDIT4 ) was detected. Knockdown and overexpression assays were used to evaluate the effect of circXPO1 on MM. Specifically, 5-ethynyl-2′-deoxyuridine and cell counting kit-8 assay were used to investigate cell proliferation. Meanwhile, flow cytometry was adopted to detect cell apoptosis and cell cycle. Apoptosis-associated and cell cycle-related proteins were detected by Western blot. Mechanistically, biotin RNA pull-down assay and dual-luciferase assay were implemented to verify the combination among miR495-3p and circXPO1 or DDIT4 . The function of circXPO1 in vivo was explored in xenograft experiments. The results showed that circXPO1 was up-regulated in both MM samples and MM cell lines and miR-495-3p was down-regulated in MM patients. Silencing circXPO1 inhibited cell proliferation, increased apoptosis rates, and caused the G1 phase arrest. Overexpression of circXPO1 yielded opposite results. In addition, RNA pull-down experiment demonstrated the interaction between circXPO1 and miR-495-3p. Silencing miR-495-3p rescued the inhibitory function caused by the knockdown of circXPO1. DDIT4 was the target of miR-495-3p. Finally, silencing circXPO1 inhibited the growth of subcutaneous tumors in vivo . In conclusion, our findings showed that circXPO1 could promote MM progression via the miR-495-3p/ DDIT4 axis.

Knockdown of circXPO1 inhibits the development of oral squamous cell carcinoma cells

Lu,

Bian,

Ferrolino

et al. 2024

Oral Diseases

BackgroundCircular RNAs (circRNAs) have emerged as pivotal regulators of cellular processes in human malignancies, including oral squamous cell carcinoma (OSCC).MethodsReverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) was used to detect RNA expression levels of circXPO1, miR‐524‐5p and cyclin D1 (CCND1). Colony formation assay and 5‐Ethynyl‐2′‐deoxyuridine (EdU) assay were performed to analyze cell proliferation, while transwell assay was carried out to investigate the cell migration and invasion. Cell apoptosis was assessed by flow cytometry. Protein expression analysis was implemented by Western blot assay. Additionally, lactate production and glucose consumption were investigated using a lactate assay kit and glucose assay kit, respectively. The in vivo tumorigenic potential of circXPO1 was evaluated using a xenograft mouse model assay.ResultsElevated levels of circXPO1 and CCND1, alongside reduced miR‐524‐5p expression were decreased in OSCC tissues and cells. Knockdown of circXPO1 in OSCC cells inhibited their proliferative, migratory and invasive capacities, as well as glycolysis, prompting apoptosis. Moreover, circXPO1 silencing hindered tumor growth in vivo. MiR‐524‐5p could be sequestered by circXPO1, and its inhibition could counteract the beneficial effects of circXPO1 knockdown on OSCC progression.ConclusionKnockdown of circXPO1 inhibited OSCC progression by up‐regulating miR‐524‐5p and down‐regulating CCND1 expression, which might provide potential targets for OSCC treatment.