title: MicroRNA-338-3p suppresses metastasis of lung cancer cells by targeting the EMT regulator Sox4.
abstract: Metastasis remains the leading cause of the majority of cancer-related mortality. MicroRNAs (miRNAs) have frequently emerged as tumor metastatic regulator by acting on multiple signaling pathways. In the present study, we demonstrated that miR-338-3p was significantly downregulated in highly metastatic NSCLC cell lines and clinical metastatic tissues. Then, we found that introduction of miR-338-3p significantly suppressed the migration and invasion of lung cancer cells both in vitro and in vivo, suggesting that miR-338-3p may be a novel tumor suppressor. Further studies indicated that the EMT-related transcription factor Sox4 was one direct target gene of miR-338-3p, evidenced by the direct binding of miR-338-3p with the 3'untranslated region (3'UTR) of Sox4. Furthermore, miR-338-3p could decrease the expression of Sox4 both at mRNA and protein levels. Notably, the EMT marker E-cadherin or vimentin, a downstream regulator of Sox4, was also down-regulated or up-regulated upon miR-338-3p treatment. Additionally, over-expressing or silencing Sox4 could elevate or inhibit the migration and invasion of lung cancer cells, parallel to the effect of miR-338-3p on the lung cancer cells. Meanwhile, knockdown of Sox4 reversed the enhanced migration and invasion mediated by miR-338-3p. These results indicated that miR-338-3p suppressed the migration and invasion of NSCLC cells through targeting Sox4 involving in the EMT process. Thus, our finding provides new insight into the mechanism of NSCLC progression. Therapeutically, miR-338-3p may serve as a potential target in the treatment of human lung cancer.
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital Tianjin 300052, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital Tianjin 300052, China.
authors.forename: Peirui
authors.initials: P
authors.lastname: Chen
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital Tianjin 300052, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zu
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital Tianjin 300052, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital Tianjin 300052, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital Tianjin 300052, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zhou
keywords: MiR-338-3p; NSCLC; metastasis; sox4