Gene SH3BGRL3 regulates acute myeloid leukemia progression through circRNA_0010984 based on competitive endogenous RNA mechanism

Xiancong Yang; Yaoyao Wang; Simin Rong; Jiayue An; Xiaoxu Lan; Baohui Yin; Yunxiao Sun; Pingyu Wang; Boyu Tan; Ye Xuan; Shuyang Xie; Zhenguo Su; Youjie Li

doi:10.3389/fcell.2023.1173491

Gene SH3BGRL3 regulates acute myeloid leukemia progression through circRNA_0010984 based on competitive endogenous RNA mechanism

Front Cell Dev Biol. 2023 Jun 12:11:1173491. doi: 10.3389/fcell.2023.1173491. eCollection 2023.

Authors

Xiancong Yang^{1

2}, Yaoyao Wang³, Simin Rong², Jiayue An^{1

2}, Xiaoxu Lan², Baohui Yin³, Yunxiao Sun³, Pingyu Wang², Boyu Tan², Ye Xuan², Shuyang Xie², Zhenguo Su¹, Youjie Li²

Affiliations

¹ Department of Clinical Laboratory, The Second Medical College of Binzhou Medical University, Yantai, China.
² Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai, China.
³ Department of Pediatrics, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China.

Abstract

Introduction: Acute myeloid leukemia (AML) is a malignant proliferative disease affecting the bone marrow hematopoietic system and has a poor long-term outcome. Exploring genes that affect the malignant proliferation of AML cells can facilitate the accurate diagnosis and treatment of AML. Studies have confirmed that circular RNA (circRNA) is positively correlated with its linear gene expression. Therefore, by exploring the effect of SH3BGRL3 on the malignant proliferation of leukemia, we further studied the role of circRNA produced by its exon cyclization in the occurrence and development of tumors. Methods: Genes with protein-coding function obtained from the TCGA database. we detected the expression of SH3BGRL3 and circRNA_0010984 by real-time quantitative polymerase chain reaction (qRT-PCR). We synthesized plasmid vectors and carried out cell experiments, including cell proliferation, cell cycle and cell differentiation by cell transfection. We also studied the transfection plasmid vector (PLVX-SHRNA2-PURO) combined with a drug (daunorubicin) to observe the therapeutic effect. The miR-375 binding site of circRNA_0010984 was queried using the circinteractome databases, and the relationship was validated by RNA immunoprecipitation and Dual-luciferase reporter assay. Finally, a protein-protein interaction network was constructed with a STRING database. GO and KEGG functional enrichment identified mRNA-related functions and signaling pathways regulated by miR-375. Results: We identified the related gene SH3BGRL3 in AML and explored the circRNA_0010984 produced by its cyclization. It has a certain effect on the disease progression. In addition, we verified the function of circRNA_0010984. We found that circSH3BGRL3 knockdown specifically inhibited the proliferation of AML cell lines and blocked the cell cycle. We then discussed the related molecular biological mechanisms. CircSH3BGRL3 acts as an endogenous sponge for miR-375 to isolate miR-375 and inhibits its activity, increases the expression of its target YAP1, and ultimately activates the Hippo signaling pathway involved in malignant tumor proliferation. Discussion: We found that SH3BGRL3 and circRNA_0010984 are important to AML. circRNA_0010984 was significantly up-regulated in AML and promoted cell proliferation by regulating miR-375 through molecular sponge action.

Keywords: Acute myeloid leukemia; Hsa_circ_0010984; SH3BGRL3; TCGA; qRT-PCR.

Grants and funding

The present study was supported by The Support Plan for Youth Entrepreneurship and Technology of Colleges and Universities in Shandong (grant nos. 2019KJK014 and 2021KJ101), The National Natural Science Foundation of China (grant nos. 81800169 and 82002604), The Shandong Science and Technology Committee (grant nos. ZR2020QH221 and ZR2022LSW002), The Foundation of Binzhou Medical University (grant no. BY2021LCX04), College Students’ Innovation and Entrepreneurship Training Program (grant nos. 202210440069 and S202210440097), The Shandong Province Taishan Scholar Project (grant no. ts201712067).