Identifying a Tumor Suppressor in Chronic Myeloid Leukemia
Posted: Friday, March 6, 2020
Increased levels of microRNA-141-5p (miR-141-5p) in patients treated with nilotinib or imatinib has been shown to act as a tumor suppressor in chronic myeloid leukemia (CML). The findings published in Frontiers in Pharmacology demonstrate the microRNA acts as a tumor suppressor by silencing RAB32, a member of the RAS oncogene family. According to Jing Bao, of Anhui Medical University, Hefei China, and colleagues: “Our study demonstrated that miR-141-5p played an important role in the activation of K562 cells…. Therefore, miR-141-5p may provide new clues for the diagnosis and novel targeted therapy of CML.”
The authors used human samples, mouse models, and leukemic cell cultures (K562) to identify miR-141-5p as a tumor suppressor. First, blood samples were collected from a total of 21 patients with CML treated with nilotinib or imatinib and from 14 healthy controls. Quantitative polymerase chain reaction revealed decreased levels of the microRNA in patients with CML versus healthy individuals. However, after 3 months of treatment, levels of miR-141-5p were upregulated. This result was also true for K562 cells, as miR-141-5p was downregulated compared with healthy CD34-positive cells.
The researchers then overexpressed miR-141-5p in K562 cells and noted these cells were found to have a reduction in proliferation and migration and an increase in apoptosis compared with control cells. Next, the authors observed tumors that stably expressed miR-141-5p grew significantly slower and were smaller after 3 weeks in nude mice than in controls.
Using bioinformatics, the group then revealed that RAB32 was upregulated in patients with CML. Inhibiting miR-141-5p in K562 cells increased expression of RAB32, whereas overexpressing miR-141-5p decreased expression, further suggesting that RAB32 is the target gene. Finally, by downregulating RAB32 in K562 cells, proliferation and migration of cells were weakened, whereas apoptosis was promoted.
Disclosure: The study authors reported no conflict of interests.