To explore the mechanism of lnc SNHG20 in the regulation of proliferation, invasion, and migration of breast cancer cells. mRNA levels of SNHG20, miR-495, and HER2 were detected by qRT-PCR. Protein level of HER2 was measured by Western blot. Cell proliferation, invasion, and migration were detected by CCK-8 assay, Boyden chamber assay, and Transwell assay. The combination between SNHG20 and miR-495 was confirmed by RNA pull down assay. The combination between miR-495 and HER2 was confirmed by luciferase report assays. We also established breast cancer-bearing mice model and analyzed tumor volumes. Our data showed SNHG20 expression was significantly upregulated, miR-495 expression was significantly downregulated, and HER2 expression was significantly upregulated in breast cancer tissues and cell lines. Besides, SNHG20 promoted the proliferation, invasion, and migration of breast cancer cells. We also found SNHG20 negatively regulated miR-495, and miR-495 could negatively regulate HER2. Moreover, we discovered that SNHG20 regulated HER2 via miR-495. SNHG20 regulated proliferation, invasion, and migration of breast cancer cells via miR-495/HER2. Finally, we confirmed the mechanism of SNHG20 in the regulation of proliferation, invasion, and migration in breast cancer-bearing mice model. SNHG20 regulates HER2 via miR-495 to promote proliferation, invasion, and migration of breast cancer cells.

OBJECTIVE: A micro-molecule peptide TP1623 of 99mTc-human epithelial growth factor receptor 2 (HER2) was prepared and the feasibility of using it as a HER2-positive molecular imaging agent for breast cancer was evaluated. METHODS: TP1623 was chemically synthesized and labeled with 99mTc. The labeling ratio and stability were detected. HER2 expression levels of breast cancer cells (SKBR3 and MDA-MB-231) and cell binding activity were measured. Biodistribution of 99mTC-TP1623 in normal mice was detected. SKBR3/MDA-MB-231-bearing nude mice models with high/low expressions of HER2 were established. Tumor tissues were stained with hematoxylin–eosin (HE) and measured by immunohistochemistry to confirm the formation of tumors and HER2 expression. SPECT imaging was conducted for HER2-overexpressing SKBR3-bearing nude mice. The T/NT ratio was calculated and compared with that of MDA-MB-231-bearing nude mice with low HER2 expression. The competitive inhibition image was used to discuss the specific binding of 99mTc- TP1623 and the tumor. RESULTS: The labeling ratio of 99mTc-TP1623, specific activity, and radiochemical purity (RCP) after 6 h at room temperature were (97.39 ± 0.23)%, (24.61 ± 0.06) TBq/mmol, and (93.25 ± 0.06)%, respectively. HER2 of SKBR3 and MDA-MB-231 cells showed high and low expression levels by immunohistochemistry, respectively. The in vitro receptor assays indicated that specific binding of TP1623 and HER2 was retained. Radioactivity in the brain was always at the lowest level, while the clearance rate of blood and the excretion rate of the kidneys were fast. HE staining showed that tumor cells were observed in SKBR3- and MDA-MB-231-bearing nude mice, with significant heteromorphism and increased mitotic count. The imaging of mice showed that targeted images could be made of 99mTc-TP1623 in high HER2-expressing tumors, while no obvious development was shown in tumors in low HER2-expressing nude mice. No development was visible in tumors in competitive inhibition of imaging, which indicates the combination of 99mTc-TP1623 and tumor was mediated by HER2. CONCLUSION: High labeling ratio and specific activity of 99mTc-TP1623 is successfully prepared; it is a molecular imaging agent for HER2-positive tumors that has potential applicative value.