Quercetin obstructs Triple Negative Breast Cancer (TNBC) progression by targeting HuR

Hu-antigen R (HuR) or embryonic lethal, abnormal vision, Drosophila (ELAV)-like protein-1 (ELAVL-1) has been implicated in various cancers [1]. HuR expression has been associated with treatment resistance of TNBCs, and impairing HuR signaling re-sensitizes TNBC cells towards chemo-as well as radiotherapies. In the present study, we investigated the clinical significance of HuR protein and it’s targeting by quercetin in breast cancer.

Using an online meta-analysis tool, we found that HuR expression positively correlated with reduced overall survival of TNBC patients. Furthermore, we showed that the TNBC breast cancer cell lines i.e., MDA-MB-231 and MDA-MB-468 are good model systems to study HuR protein, as they both exhibit a significant amount of cytoplasmic HuR (active form). We showed that quercetin treatment significantly inhibited the cytoplasmic HuR in both TNBC cell lines.

By using specific HuR siRNA, we established that quercetin-mediated inhibition of adhesion and migration of TNBC cells is dependent on HuR. Overall, the present results demonstrate that increased HuR levels are associated with TNBC progression and relapse, and the ability of quercetin to inhibit active HuR protein provides a rationale for using it as an anticancer agent for the treatment of aggressive TNBCs.

Publikationsverlauf

Artikel online veröffentlicht:
13. Dezember 2021

• References

• 1 Wang J, Guo Y, Chu H, Guan Y, Bi J. et al. Multiple functions of the RNA-binding protein HuR in cancer progression, treatment responses and prognosis. Int J Mol Sci 2013; 14 (05) 10015-10041