Circular RNA hsa_circRNA_002178 silencing retards breast cancer progression via microRNA-328-3p-mediated inhibition of COL1A1

Ting Liu; Ping Ye; Yuanyuan Ye; Sen Lu; Baosan Han

doi:10.1111/jcmm.14875

Circular RNA hsa_circRNA_002178 silencing retards breast cancer progression via microRNA-328-3p-mediated inhibition of COL1A1

J Cell Mol Med. 2020 Feb;24(3):2189-2201. doi: 10.1111/jcmm.14875. Epub 2020 Jan 19.

Authors

Ting Liu^{1

2

3}, Ping Ye⁴, Yuanyuan Ye^{1

2

3}, Sen Lu^{1

2

3}, Baosan Han^{1

2

3}

Affiliations

¹ Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, China.
⁴ School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, China.

Abstract

Circular RNAs (circRNAs) are a group of non-coding RNAs implicated in the pathogenesis of cancer progression, which exert their functions via regulation of microRNAs (miRNAs) and genes. The present study uses gain- and loss-of-function approaches to evaluate the functions of hsa_circRNA_002178 in angiogenesis along with energy metabolism and underlying downstream signals. The expression pattern of hsa_circRNA_002178 in clinical breast cancer tissues and its association with prognosis were characterized at first. Next, the energy metabolism and angiogenesis as well as cell viability were evaluated when the expression of hsa_circRNA_002178 in breast cancer cells was knocked down by siRNA. The interaction between hsa_circRNA_002178 and its downstream miR-328-3p was identified, followed by the analysis of their functions in regulation of breast cancer cellular behaviours. The target gene of miR-328-3p was predicted and verified, followed by identifying its role in the breast cancer progression. Higher expression of hsa_circRNA_002178 shared an association with worse prognosis in breast cancer. The inhibition of hsa_circRNA_002178 resulted in reductions in cell viability, energy metabolism and tube formation ability. Hsa_circRNA_002178 could competitively bind to miR-328-3p and down-regulated its expression. Restoration of miR-328-3p eliminated the tumour-promoting effects of hsa_circRNA_002178. COL1A1, as a target of miR-328-3p, could be up-regulated by overexpression of hsa_circRNA_002178. In vivo experiments further confirmed the inhibition of tumour growth and inflammation by silencing hsa_circRNA_002178 or up-regulating miR-328-3p. Taken together, hsa_circRNA_002178 is highlighted as a promising target for breast cancer due to the anti-tumour effects achieved by silencing hsa_circRNA_002178.

Keywords: COL1A1; Hsa_circRNA_002178; MicroRNA-328-3p; angiogenesis; breast cancer; circular RNA; energy metabolism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Animals
Breast / pathology
Breast Neoplasms / genetics*
Breast Neoplasms / pathology
Cell Line
Cell Line, Tumor
Cell Survival / genetics
Collagen Type I / genetics*
Collagen Type I, alpha 1 Chain
Disease Progression
Down-Regulation / genetics
Female
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
MicroRNAs / genetics*
Neovascularization, Pathologic / genetics
Neovascularization, Pathologic / pathology
RNA Interference / physiology*
RNA, Circular / genetics*
RNA, Small Interfering / genetics
Up-Regulation / genetics

Substances

Collagen Type I
Collagen Type I, alpha 1 Chain
MIRN328 microRNA, human
MicroRNAs
RNA, Circular
RNA, Small Interfering