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.