Eur Rev Med Pharmacol Sci 2019; 23 (13): 5823-5830

DOI: 10.26355/eurrev_201907_18321

MiR-296-3p may affect the proliferation and migration of non-small cell lung cancer cells via regulating RABL3

T. Ge, H.-C. Wu, Y.-Y. Zhou, S.-M. Shen, L.-G. Zhu, G.-X. You

Respiratory Department, Ningbo City Medical Treatment Center Lihuili Hospital, Ningbo, China. qo8e34@163.com


OBJECTIVE: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. The pathogenesis of NSCLC has not yet been fully understood, and the therapeutic efficacy of current anti-NSCLC medication remains unsatisfactory. Previous studies indicated that miR-296-3p was down-regulated in NSCLC, suggesting that miR-296-3p may participate in the pathogenesis of NSCLC; however, the specific mechanisms still need to be further explored. The aim of this work is to investigate the roles of miR-296-3p in NSCLC and the related mechanism.

PATIENTS AND METHODS: Thirty NSCLC tissue and paired adjacent tissue were collected, and Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was performed to examine the expression of miR-296-3p in cancer tissue and the adjacent tissue. Next, A549 cells were cultured and transfected with miR-296-3p mimics, and cell migration and invasion were determined using scratch wound-healing and transwell assays. Moreover, Western blot assay was performed to determine the effect of miR-296-3p on the expression of Rab-like 3 (RABL3), Matrix metallopeptidase (MMP)-2, Janus kinase (JAK) and Signal transducer and activator of transcription 3 (STAT3); next, Dual-Luciferase reporter assay has been conducted to prove the direct targeting relationship between miR-296-3p and RABL3. Finally, the cells of different treatments were subcutaneously implanted into nude mice to investigate the effect of miR-296-3p mimics in the xenograft mice tumor models.

RESULTS: Our data indicated that miR-296-3p was significantly down-regulated and RABL3 was markedly up-regulated in NSCLC tissue compared with the adjacent tissue. Moreover, transient over-expression of miR-296-3p in A549 cells induced a significant decrease in the proliferation and invasion ability of A549 cells, as well as decreased expression of RABL3, MMP-2, JAK and STAT3. Furthermore, the Dual-Luciferase reporter assay confirmed that RABL3 is a direct target of miR-296-3p. Finally, the results of animal studies indicated that miR-296-3p can regulate the tumorigenesis of A549 cells in vivo.

CONCLUSIONS: Our findings proved that miR-296-3p may play a role as a tumor suppressor in NSCLC both in vitro and in vivo, and we first reported that miR-296-3p can regulate the migration and invasion of A549 cells via targeting RABL3. Our data suggested that miR-296-3p may serve as a potential therapeutic target for treating NSCLC.

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To cite this article

T. Ge, H.-C. Wu, Y.-Y. Zhou, S.-M. Shen, L.-G. Zhu, G.-X. You
MiR-296-3p may affect the proliferation and migration of non-small cell lung cancer cells via regulating RABL3

Eur Rev Med Pharmacol Sci
Year: 2019
Vol. 23 - N. 13
Pages: 5823-5830
DOI: 10.26355/eurrev_201907_18321