miR-302 Suppresses the Proliferation, Migration, and Invasion of Breast Cancer Cells by Downregulating ATAD2

Abstract

Breast cancer is the most common malignant tumor in women. The ATPase family AAA domain-containing protein 2 (ATAD2) contains an ATPase domain and a bromodomain, and is abnormally expressed in various human cancers, including breast cancer. However, the molecular mechanisms underlying the regulation of ATAD2 expression in breast cancer remain unclear. This study aimed to investigate the expression and function of ATAD2 in breast cancer. We found that ATAD2 was highly expressed in human breast cancer tissues and cell lines. ATAD2 depletion via RNA interference inhibited the proliferation, migration, and invasive ability of the SKBR3 and T47D breast cancer cell lines. Furthermore, Western blot analysis and luciferase assay results revealed that ATAD2 is a putative target of miR-302. Transfection with miR-302 mimics markedly reduced cell migration and invasion. These inhibitory effects of miR-302 were restored by ATAD2 overexpression. Moreover, miR-302 overexpression in SKBR3 and T47D cells suppressed tumor growth in the xenograft mouse model. However, ATAD2 overexpression rescued the decreased tumor growth seen after miR-302 overexpression. Our findings indicate that miR-302 plays a prominent role in inhibiting the cancer cell behavior associated with tumor progression by targeting ATAD2, and could thus be a valuable target for breast cancer therapy.

The miR‐302/367 cluster: Aging, inflammation, and cancer

“…81 By specifically targeting ATAD2, the miR-302 family inhibits the biologically harmful activity of cells and tumor formation in mice. 82 Aspirin promotes the EMT state, stimulates miR-302/367-induced BC cell reprogramming, and suppresses the expression of angiogenic and invasion markers. Without changing its ability to inhibit cell growth, aspirin increases the extent of apoptosis brought on by miR-302/ 367 clusters.…”

“…118 The authors also noted that clinical specimens can be used to study the miR-217-ATAD2-AKT axis to add to the evidence for the treatment of pancreatic cancer. 118 MiR-302 can target ATAD2 to promote malignant behavior and cisplatin sensitivity in BC cells 82 and OC cisplatin-resistant cells. 87 It will be interesting to see whether the miR-302/ATAD2 axis can regulate other types of cancer as a biological therapeutic target to increase cancer treatment.…”

“…MiR‐302 directly and functionally targets MAP/ERK kinase kinase 1 (MEKK1), which inhibits P‐gp by selectively targeting MEKK1 of the ERK pathway and makes BC cells more sensitive to the antibiotic adriamycin 81 . By specifically targeting ATAD2, the miR‐302 family inhibits the biologically harmful activity of cells and tumor formation in mice 82 . Aspirin promotes the EMT state, stimulates miR‐302/367‐induced BC cell reprogramming, and suppresses the expression of angiogenic and invasion markers.…”