Scientific Update - Circular RNA (circZNF215) in cholangiocarcinoma: A new possible therapeutic target

About 98% of the human genome is non-coding, meaning it does not contain the genetic code to make proteins. However, these non-coding regions are not “junk DNA.” Instead, they contain important regulatory elements that can affect gene expression, protein levels, and protein activity.

One type of non-coding element is circular RNAs, and a recent study in cholangiocarcinoma identified a novel circular RNA called circZNF215. The study found that circZNF215 was expressed at high levels in intrahepatic cholangiocarcinoma and associated with metastasis. Accordingly, circZNF215 was found to promote proliferation and metastasis in cell culture and animal models.
Providing mechanistic insight, the study also showed that circZNF215 blocked the interaction between PRDX1 and PTEN proteins. This inactivated the PTEN pathway, thereby promoting tumor growth. The authors thus hypothesized that silencing circZNF215 could slow tumor growth. In vitro and in vivo models supported this paradigm, and circZNF215 was also shown to increase the antitumor activity of ipatasertib, a targeted cancer therapy.
Although still early-stage research, these results are highly promising and could pave the road for novel drugs targeting circZNF215. These drugs could create new treatment options and ultimately improve outcomes for cholangiocarcinoma patients.

Reference: Liao, W., Du, J., Li, L. et al. CircZNF215 promotes tumor growth and metastasis through inactivation of the PTEN/AKT pathway in intrahepatic cholangiocarcinoma. J Exp Clin Cancer Res 42, 125 (2023). https://doi.org/10.1186/s13046-023-02699-w

Kelly Butler is an NIH Postbac Research Fellow and the Founding Director of SAFE