LncRNA FOXD3-AS1 promotes breast cancer progression by mediating ARF6

Background Breast cancer is one of the most common malignant tumor in women. The high metastatic characteristics cause a high mortality rate of breast cancer. Increasing number of studies have indicated that long non-coding RNAs (lncRNAs) play key roles in the progression of human cancers including breast cancer. In this study, we studied the expression and molecular mechanisms of lncRNA FOXD3-AS1 in breast cancer. Methods The expression of lncRNA FOXD3-AS1 was analyzed by TCGA database and RT-qPCR assay. CCK8 assay was used to measure cell proliferation ability. Cell migration and invasion capacities were detected by transwell assay. Potential targets of lncRNA and miRNA were predicted by bioinformatic tools. The targeting relationship between genes was verified by dual-luciferase reporter assay. The nude mice tumor model was performed to study the effect of FOXD3-AS1 on breast cancer in vivo. Protein expression was detected by western blot. Results In the present study, we found that the FOXD3-AS1 expression was significantly increased in breast cancer tissues compared with normal tissues and involved in the poor prognosis of patients. Functionally, knockdown of FOXD3-AS1 suppressed cell proliferation and metastasis abilities in vitro, and tumor growth in vivo. Mechanistically, FOXD3-AS1 functioned as a competing endogenous RNA (ceRNA) to upregulate ARF6 expression by targeting miR-127-3p. In addition, the roles of FOXD3-AS1 on cell proliferation and metastasis were achieved through miR-127-3p/ARF6 axis. Conclusion In summary, our results reported the regulatory mechanism of FOXD3-AS1 in breast cancer progression by targeting miR-127-3p/ARF6 axis to affect cell proliferation, migration, invasion and tumor growth.

Automated summary

This study reveals that FOXD3-AS1 is significantly upregulated in breast cancer and is associated with poor prognosis. The knockdown of FOXD3-AS1 suppresses cell proliferation and metastasis in vitro, as well as tumor growth in vivo. Mechanistically, FOXD3-AS1 functions as a competing endogenous RNA to upregulate ARF6 expression by targeting miR-127-3p. The findings suggest that FOXD3-AS1 plays a crucial role in breast cancer progression.