Hyper-expressed BCYRN1 promotes proliferation and brain metastasis of Small Cell Lung Cancer by miR-378c/AJM1 axis

Abstract

Background: The purpose of this study is to explore the functions and mechanism of brain cytoplasmic RNA1 (BCYRN1) in proliferation and brain metastasis of small cell lung cancer (SCLC) cells.

Methods: The BCYRN1 levels in SCLC cell lines and serums of patients were measured via quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR). The downstream miRNA of BCYRN1 and downstream gene of miR-378c were predicted with StarBase software, and was verified by dual-Luciferase reporter assay. Colony formation assay, MTT assay, wound healing assay and transwell assay were performed to examine the influences of BCYRN1/miR-378c/AJM1 on the proliferation, migration and invasion abilities SCLC cells. The protein levels of proliferation marker Ki-67 and key proteins of epithelial-mesenchymal transition (EMT) (E-cadherin, N-cadherin, Vimentin, Snail, Slug) were detected by western blot. Animal model of brain metastasis was conducted to verify in vitro.

Results: The levels of BCYRN1 was upregulated in SCLC cell lines and serum of SCLC patients. BCYRN1 knockdown inhibited the proliferation, migration and invasion, Ki-67 expression and EMT of SCLC cells. The miR-378c was identified as a direct target of BCYRN1 in SCLC cells. Knockdown of BCYRN1 suppressed Ki-67 expression and EMT by up-regulating miR-378c, thereby inhibiting the proliferation, migration and invasion of SCLC cells. AJM1 was identified as a direct target of miR-378c. Knockdown of AJM1 reversed the effects of miR-378c knockdown on SBC-2 cells. BCYRN1 knockdown inhibited EMT on brain metastasis of SCLC cells in nude mice, but knockdown of miR-378c could reverse it.

Conclusion: Hyper-expressed BYNRN1 could promote proliferation and brain metastasis of SCLC cells by miR-378c/AJM1 axis.