Silencing SCAMP1-TV2 Inhibited the Malignant Biological Behaviors of Breast Cancer Cells by Interaction With PUM2 to Facilitate INSM1 mRNA Degradation

Wei Tao; Jun Ma; Jian Zheng; Xiaobai Liu; Yunhui Liu; Xuelei Ruan; Shuyuan Shen; Lianqi Shao; Jiajia Chen; Yixue Xue

doi:10.3389/fonc.2020.00613

Silencing SCAMP1-TV2 Inhibited the Malignant Biological Behaviors of Breast Cancer Cells by Interaction With PUM2 to Facilitate INSM1 mRNA Degradation

Front Oncol. 2020 May 27:10:613. doi: 10.3389/fonc.2020.00613. eCollection 2020.

Authors

Wei Tao^{1

2

3}, Jun Ma^{1

2

3}, Jian Zheng^{4

5

6}, Xiaobai Liu^{4

5

6}, Yunhui Liu^{4

5

6}, Xuelei Ruan^{1

2

3}, Shuyuan Shen^{1

2

3}, Lianqi Shao^{1

2

3}, Jiajia Chen^{1

2

3}, Yixue Xue^{1

2

3}

Affiliations

¹ Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang, China.
² Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang, China.
³ Key Laboratory of Medical Cell Biology, Ministry of Education of China, China Medical University, Shenyang, China.
⁴ Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China.
⁵ Liaoning Clinical Medical Research Center in Nervous System Disease, Shenyang, China.
⁶ Key Laboratory of Neuro-Oncology in Liaoning Province, Shenyang, China.

Abstract

Background: Molecular-targeted therapy plays an important role in the combined treatment of breast cancer. Long noncoding RNA (LncRNA) plays a significant role in regulating breast cancer progression. The present study is to reveal the potential roles and molecular mechanism that the secretory carrier-associated membrane protein 1-transcript variant 2 (SCAMP1-TV2) has in breast. Methods: Cell Counting Kit-8 (CCK-8), RNA Immunoprecipitation (RIP), and RNA pull-down assays were employed to determine the interactions between SCAMP1-TV2 and Pumilio RNA binding family member 2 (PUM2). The luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays were used to get to know the effect of human insulinoma-associated 1 (INSM1) directly on the SAM and SH3 domain containing 1 (SASH1) promoter. Results: Silenced SCAMP1-TV2 inhibited the proliferation, migration, and invasion of breast cancer cells, and promoted cell apoptosis. Meanwhile, SCAMP1-TV2 downregulation decreased its binding to PUM2 and increased the binding of PUM2 to INSM1 messenger RNA (mRNA), thus promoting the degradation of INSM1 mRNA. Silencing INSM1 decreased its inhibitory effect on SASH1 transcription and inhibited the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. The xenograft tumor growth in a nude mice was significantly inhibited by the silencing of SCAMP1-TV2 in combination with the overexpression of PUM2. Conclusions: SCAMP1-TV2/PUM2/INSM1 pathway plays an important role in regulating the biological behavior of breast cancer cells.

Keywords: PUM2; RNA binding protein (RBP); SCAMP1-TV2; breast cancer; lncRNA; mRNA degradation.