Cancer Management and Research (Sep 2020)
Long Noncoding RNA SNHG7 Accelerates Proliferation, Migration and Invasion of Non-Small Cell Lung Cancer Cells by Suppressing miR-181a-5p Through AKT/mTOR Signaling Pathway
Abstract
Liping Li, Dan Ye, Liang Liu, Xiaoju Li, Jun Liu, Shengtian Su, Wenjing Lu, Zhigao Yu Department of Oncology, Xiantao First People’s Hospital, Xiantao, Hubei, People’s Republic of ChinaCorrespondence: Zhigao YuDepartment of Oncology, Xiantao First People’s Hospital, No. 29, Middle Section of Mianzhou Avenue, Xiantao, Hubei 433000, People’s Republic of ChinaTel +86 13477410999Email [email protected]: Non-small cell lung cancer (NSCLC) is a typical epithelial lung cancer with high metastasis, incidence and mortality. In recent years, long noncoding RNA small nucleolar RNA host gene 7 (SNHG7) has been identified as significant regulator in different cancer types, including NSCLC. However, the underlying molecular mechanism of SNHG7 during NSCLC tumorigenesis and progression remains largely unclear.Methods: SNHG7 and miR-181a-5p expression in NSCLC tumors and cells were detected by qRT-PCR. Cell viability, migration, invasion and apoptosis were evaluated by CCK-8, transwell and flow cytometry assay, respectively. A549 and NCI-H1299 xenograft mice model was constructed by subcutaneously injecting cells stably transfected with sh-SNHG7 and sh-NC. The interaction between SNHG7 and miR-181a-5p was validated by luciferase reporter system, RIP and RNA pull down assay. Protein expression of cleaved caspase 3, proliferating cell nuclear antigen (PCNA), AKT, p-AKT, mammalian target of rapamycin (mTOR) and p-mTOR was analyzed by Western blot.Results: SNHG7 expression was up-regulated while miR-181a-5p expression was down-regulated in NSCLC tumors, especially those from patients at Phase III+IV, compared with normal tissues. However, SNHG7 depletion attenuated tumor growth in vitro and in vivo. Moreover, miR-181a-5p inhibitor abolished SNHG7 silencing induced inhibition on proliferation, migration and invasion in NSCLC. Subsequently, we found SNHG7 modulated cell progression by targeting miR-181a-5p and activating AKT/mTOR signaling pathway.Conclusion: SNHG7 accelerates proliferation, migration and invasion of NSCLC by suppressing miR-181a-5p through AKT/mTOR signaling pathway, thus presenting desirable biomarkers for NSCLC therapy.Keywords: NSCLC, SNHG7, miR-181a-5p, AKT/mTOR pathway, progression
