Journal
ANNALS OF TRANSLATIONAL MEDICINE
Volume 10, Issue 6, Pages -Publisher
AME PUBLISHING COMPANY
DOI: 10.21037/atm-22-345
Keywords
Non-small cell lung cancer (NSCLC); miR-328-5p; lysyl oxidase like 4 (LOXL4)
Categories
Funding
- National Science Foundation of China [81673840, 81803877, 81873205]
- Natural Science Foundation of Guangdong Province, China [2020B1515120063]
- Guangdong Basic and Applied Basic Research Foundation, China [2020A1515110651]
- Social science and Technology Development Foundation of Dongguan [202050715001207]
- Medical Scientific Research Foundation of Guangdong Province, China [20201151015201]
- Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine [ZYYCXTD-C-202001]
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This study found that miR-328-5p promotes proliferation and migration of NSCLC cells by targeted regulation of LOXL4.
Background: Lung cancer is the leading cause of cancer-associated mortality worldwide, and most lung cancers are classified as non-small cell lung cancer (NSCLC). MiR-328 influence the progression of multiple tumors, but the role of miR-328-5p in NSCLC has not been elucidated. The aim of this study was to illuminate the oncogenic role and potential molecular mechanisms of the miR-328-5p and lysyl oxidase like 4 (LOXL4) in NSCLC. Methods: Expression of miR-328-5p was detected by real-time quantitative polymerase chain reaction (qRT-PCR) in tumor and non-tumor adjacent tissues. After Lentivirus-miR-328-5p was employed to intervene this miRNA in NSCLC cell lines, RT-qPCR was used to detect the expression levels of miR-3285p. Cell Counting Kit-8 (CCK-8), cell colony formation, flow cytometry, wound healing, Transwell assays were used to determine the malignant phenotypes of NSCLC cells. Nude mice models of subcutaneous tumors were established to observe the effect of miR-328-5p on tumorigenesis. Targeting the 3'UTR of LOXL4 by miR-328-5p was verified by integrated analysis including transcriptome sequencing, dualluciferase and western-blot assays. Results: High miR-328-5p level was observed in NSCLC cells from The Cancer Genome Atlas (TCGA) database and tumor tissues collected from NSCLC patients. Overexpressed miR-328-5p promoted NSCLC cell proliferation, survival, and migration, and promoted tumor growth in vivo. Knockdown of miR328-5p suppressed tumorigenic activities. Transcriptome sequencing analysis revealed that LOXL4 was downregulated by miR-328-5p, which was confirmed by dual-luciferase reporter and western-blot assays. Conclusions: miR-328-5p showed targeted regulation of LOXL4 to promote cell proliferation and migration in NSCLC.
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