Long non-coding RNA CASC7 suppresses malignant behaviors of breast cancer by regulating miR-21-5p/FASLG axis

ABSTRACT

Recently, it has been increasingly proved that lncRNAs are functionally involved in a majority of tumor progression. LncRNA CASC7 has also been revealed to participate in the development of several cancers as a tumor promoter or suppressor. Herein, we focus on uncovering the role and underlying molecular mechanism of CASC7 in breast cancer. Tumor tissues and the paired paracancerous tissues from the breast cancer patients were used to evaluate the level of CASC7 in breast cancer. By analyzing the CASC7 expression in breast cancer cell lines, both the expression levels of CASC7 in cancer tissues and cell lines were obviously downregulated compared to those in paired paracancerous tissues and normal human epithelial MCF10A cells. Subsequently, the construction of lentivirus overexpression system (oe-CASC7 and oe-NC) was used to elevate the expression of CASC7. A series of functional experiments were conducted to show that the cell proliferation, migration, and invasion were inhibited when CASC7 overexpressed in breast cancer cells. Meanwhile, the apoptosis of oe-CASC7 cells was induced compared to the oe-NC breast cancer cells. We further confirmed that CASC7 functions by regulating miR-21-5p/FASLG axis. Finally, a xenograft model in nude mice verified that CASC7 was a tumor suppressor in breast cancer. These results suggest that lncRNA CASC7 suppresses to malignant behaviors of breast cancer by modulating miR-21-5p/FASLG axis. Abbreviations lncRNAs: long non-coding RNAs; ceRNA: competing endogenous RNA; CASC7: cancer susceptibility candidate 7; miRNAs: MicroRNAs; MAPK10: mitogen-activated protein kinase 10; FASLG: Tumor Necrosis Factor Ligand Superfamily Member 6; FAS: Tumor Necrosis Factor Receptor Superfamily Member 6

KEYWORDS:

• lncRNA CASC7
• miR-21-5p
• FASLG
• breast cancer

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethics and consent statement

This study was performed with the approval of the Research Ethics Committee of Hubei University of Medicine. In addition, written informed consent forms were signed by all the patients who participated in this research. All animal experiments were performed with the approval of the animal ethics committee of Hubei University of Medicine and conducted according to the guidelines set forth in the National Institutes of Health’s (NIH) ‘Guide for the Care and Use of Laboratory Animals’ (8th edition).

Additional information

Funding

This work was supported by the research grants from the National Natural Science Foundation of China [Grants number: 81901567], the Natural Science Foundation of Hubei Province [Grants number: 2018CFB112], the Natural Science Foundation of Hubei Provincial Department of Education [Q20202105], the Cultivating Project for Young Scholar at Hubei University of Medicine [Grants number: 2017QDJZR07], and the Scientific and Technological Project of Shiyan City of Hubei Province [Grants number: 19Y03].