Abstract
Retinoblastoma is a rare ocular tumor in children that originates in the retina. Several core transcriptional regulators maintain the expansion of retinoblastoma tumors, including c-Myc. Here, we demonstrated that Helicase with zinc finger domain 2 (HELZ2) promoted retinoblastoma tumorigenesis by targeting c-Myc. HELZ2-deficient inhibited retinoblastoma cell proliferation, whereas overexpression of HELZ2 promoted retinoblastoma cell proliferation. In addition, high levels of HELZ2 promoted xenograft retinoblastoma tumorigenesis and inhibited animal survival. Mechanistically, HELZ2 interacted with c-Myc and promoted its K63-linked polyubiquitination. We indicated that HELZ2 promoted the interaction between E3 ubiquitin ligase HUWE1 and c-Myc, and HELZ2-mediated K63-linked polyubiquitination and activation of c-Myc were dependent on HUWE1. Taken together, HELZ2 plays a critical role in the regulation of retinoblastoma tumorigenesis by enhancing the activity of c-Myc.
Highlights
Retinoblastoma was first described by Pawius in the sixteenth century [1]
We found that Helicase with zinc finger domain 2 (HELZ2) deficiency inhibited retinoblastoma cell proliferation, while cell growth was restored after rescuing HELZ2 (Fig. 1d and e)
We demonstrated that HELZ2 plays a critical role in c-Myc-associated retinoblastoma tumorigenesis
Summary
Retinoblastoma was first described by Pawius in the sixteenth century [1]. Retinoblastoma is the most common intraocular malignancy in children, accounting for 3% of all childhood cancers [2]. The annual incidence rate of newborns worldwide is around 1 in 12000 to 1 in 20000, and the incidence rate of retinoblastoma continues to increase [4]. According to the different conditions observed by the patient, retinoblastoma can be treated in many methods, such as enucleation, radiotherapy, chemotherapy and cryotherapy [6]. There are still many shortcomings in the treatment of high-risk retinoblastoma recurrence. Indepth exploration of the intracellular signal transmission mechanism of retinoblastoma is essential to discover potential therapeutic targets
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