circFBXW7 Inhibits Malignant Progression by Sponging miR-197-3p and Encoding a 185-aa Protein in Triple-Negative Breast Cancer

Abstract

Accumulating evidence indicates that circular RNAs (circR-NAs) are vital regulators of various biological functions involved in the progression of multiple cancers. Circular F-box and WD repeat domain containing 7 (circFBXW7) (hsa_circ_0001451) has been reported to act as a tumor suppressor by encoding a novel protein in glioma; however, its functions and mechanisms in triple-negative breast cancer (TNBC) remain elusive. In the current study, we validated by qRT-PCR that circFBXW7 was downregulated in TNBC cell lines and found that low expression of circFBXW7 was associated with poorer clinical outcomes. circFBXW7 expression was negatively correlated with tumor size and lymph node metastasis, and it was an independent prognostic factor for TNBC patients. We performed cell proliferation, colony formation, transwell, wound-healing, and mouse xenograft assays to confirm the functions of circFBXW7. Overexpression of circFBXW7 obviously inhibited cell proliferation, migration, and tumor growth in both in vitro and in vivo assays. Luciferase reporter assays and RNA immunoprecipitation assays revealed that circFBXW7 serves as a sponge of miR-197-3p and suppresses TNBC growth and metastasis by upregulating FBXW7 expression. In addition, the FBXW7-185aa protein encoded by circFBXW7 inhibited the proliferation and migration abilities of TNBC cells by increasing the abundance of FBXW7 and inducing c-Myc degradation. In summary, our research demonstrated that circFBXW7 sponges miR-197-3p and encodes the FBXW7-185aa protein to suppress TNBC progression through upregulating FBXW7 expression. Thus, circFBXW7 may act as a therapeutic target and prognostic biomarker for TNBC.

TUSC8 inhibits the development of osteosarcoma by sponging miR‑197‑3p and targeting EHD2

“…As expected, the interaction between miR-197-3p and TUSc8 was confirmed by luciferase reporter and RIP assays. According to previous studies, miR-197-3p plays an oncogenic role in breast cancer, bladder cancer and thyroid cancer (19,20,42,43). However, the anti-oncogenic role of miR-197-3p has been found in prostate cancer and gastric cancer (44,45).…”

circGNB1 Facilitates Triple-Negative Breast Cancer Progression by Regulating miR-141-5p-IGF1R Axis

“…Similarly, circRNA can also act as a tumor suppressor in the development and progression of cancer. For example, circFBXW7 inhibits tumor growth and metastasis in glioma and breast cancer by encoding a 21kDa novel protein FBXW7-185aa and blocking miR-197-3p Ye et al, 2019). circMTO1 suppresses malignancy progression by serving as the sponge of oncogenic miR-9 to upregulate p21 expression in human hepatocellular carcinoma (Han et al, 2017).…”

Translation and functional roles of circular RNAs in human cancer

“…It interacts competitively with the deubiquitinating enzyme USP28, which antagonizing USP28-induced c-Myc stabilization. Another recent work demonstrated that FBXW7-185aa can inhibit the proliferation and migration of triple-negative breast cancer cells by increasing the abundance of FBXW7 and inducing c-Myc degradation [103].…”