Circular RNA (circ‐0075804) promotes the proliferation of retinoblastoma via combining heterogeneous nuclear ribonucleoprotein K (HNRNPK) to improve the stability of E2F transcription factor 3 E2F3

Abstract

It is growingly recognized that messenger RNAs (mRNAs) are important regulators of various cancers. However, there are few reporters about the function of E2F3 in retinoblastoma (RB), which needs more exploration. In addition, the circRNA circ-0075804 was derived from the E2F3 host gene. The purpose of the study is to figure out the role and molecular regulation mechanism of E2F3 and circ-0075804 in RB. The role of E2F3 in RB was determined through E2F3 silencing and loss of expression was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR), Western blot, CCK-8, colony formation, and 5-ethynyl-2′-deoxyuridine assays. The interactions between E2F3 and circ-0075804 were validated through loss and gain function of circ-0075804. Besides, the role of circ-0075804 in RB was determined by several functional assays. And the binding ability between heterogeneous nuclear ribonucleoprotein K and circ-0075804 was verified by RNA pull-down, Western blot, and RT-qPCR assays. The expression of E2F3 was upregulated in RB cell lines. Furthermore, knockdown of E2F3 inhibited cell proliferation and induced cell apoptosis in RB. And circ-0075804 positively regulated the expression of E2F3. Moreover, circ-0075804 facilitated cell proliferation and suppressed cell apoptosis. Besides, HNRNPK could bind with circ-0075804 in RB. Finally, knockdown of E2F3 partly rescued the promoting role of circ-0075804 overexpression in RB. Overall, circ-0075804 promotes the proliferation of RB via combining HNRNPK to improve the stability of E2F3, which brings new light for treating RB. K E Y W O R D S circ-0075804, E2F3, HNRNPK, retinoblastoma

CircRNA Is a Rising Star in Researches of Ocular Diseases

“…In another study, circ_0075804 and its homologous mRNA derived from gene E2F3 were highly expressed in RB cells (Zhao et al, 2020). Interestingly, circ_0075804 was found to enhance the stability of E2F3 mRNA with the help of HNRNPK (a type of RBP) (Zhao et al, 2020). Thus, the level of E2F3 mRNA and coding protein was upregulated by circ_0075804, but E2F3 had no impact on circ_0075804 (Zhao et al, 2020).…”

“…Furthermore, overexpressed circ_0001649 was shown to inhibit the proliferative ability of RB cells by modulating the signaling pathway of AKT/mTOR and slow down the xenograft growth of RB in the mouse model (Xing et al, 2018). In another study, circ_0075804 and its homologous mRNA derived from gene E2F3 were highly expressed in RB cells (Zhao et al, 2020). Interestingly, circ_0075804 was found to enhance the stability of E2F3 mRNA with the help of HNRNPK (a type of RBP) (Zhao et al, 2020).…”

“…Interestingly, circ_0075804 was found to enhance the stability of E2F3 mRNA with the help of HNRNPK (a type of RBP) (Zhao et al, 2020). Thus, the level of E2F3 mRNA and coding protein was upregulated by circ_0075804, but E2F3 had no impact on circ_0075804 (Zhao et al, 2020). The silencing of circ_0075804 can lead to downregulated E2F3 and then inhibit its proliferation, promote apoptosis of RB cells, and slow down RB progression (Zhao et al, 2020).…”

“…Thus, the level of E2F3 mRNA and coding protein was upregulated by circ_0075804, but E2F3 had no impact on circ_0075804 (Zhao et al, 2020). The silencing of circ_0075804 can lead to downregulated E2F3 and then inhibit its proliferation, promote apoptosis of RB cells, and slow down RB progression (Zhao et al, 2020). Lyu et al (2019) found that there was a correlation between the parental genes of dysregulated circRNAs in RB samples and the function of chromatin modification, which is an important part of the pathogenesis of RB.…”

“…In recent years, more and more circRNAs have been revealed to be involved in special characteristics of cancer, including resistance to cell death, limitless replication, sustained angiogenesis, tissue invasion, and metastasis (Su et al, 2019). Here, except for normal sponging miRNAs, circRNAs such as circ_0075804 can also perform oncogenesis regulation in cells by interacting with RBPs (Zhao et al, 2020). Listed studies reveal a novel scale of the role of circRNAs in ocular malignancy pathogenesis.…”