miR-139 targets CXCR4 and inhibits the proliferation and metastasis of laryngeal squamous carcinoma cells

Abstract

Our previous studies have showed that chemokine receptor 4 (CXCR4) was over-expressed in laryngeal squamous cell carcinoma (LSCC). However, the mechanism underlying aberrant CXCR4 expression remains unclear. To investigate the roles played by miRNAs in CXCR4 over-expression in LSCC, putative miR-139 was predicted through computational algorithms, including TargetScan, PicTar and miRBase, and luciferase reporter assay was explored to confirm that whether CXCR4 was directly regulated by miR-139. Then, quantitative real-time PCR, immunohistochemistry and in situ hybridization methods were employed to detect the expression of miR-139 and CXCR4 in primary LSCC tissues, normal adjacent mucosal tissues and metastatic lesions derived from 40 LSCC patients in the Second Hospital, Xi'An JiaoTong University. Finally, gain- and loss-of-function assays were adopted to explore the effects of miR-139 and CXCR4 on proliferation, invasion and metastasis of the human LSCC cell line Hep-2 in vitro and in vivo. Our results showed that miR-139 dampened CXCR4 expression, and CXCR4 was directly targeted by miR-139. Additionally, the expression of miR-139 was reduced in alignment with the progression of primary to metastatic LSCC. Moreover, an inverse correlation was observed between miR-139 and CXCR4 protein levels in LSCC specimens. Functional analyses demonstrated that ectopic expression of miR-139 inhibited cell proliferation, migration and metastasis of Hep-2 cells in vitro and in vivo. Similar to the observations seen in restoring miR-139 expression, dampening of CXCR4 expression inhibited cell growth, migration and invasion, whereas miR-139 over-expression reversed the pro-metastatic effect of CXCR4. Taken together, we conclude that miR-139 targets CXCR4 and inhibits proliferation and metastasis of LSCC.

MicroRNA‑139 inhibits the proliferation, migration and invasion of gastric cancer cells by directly targeting ρ‑associated protein kinase 1

“…Additionally, miR-139 suppresses epithelial-mesenchymal transition, migration and invasion in hepatocellular carcinoma, and the incidence and severity of pulmonary metastasis in orthotopic liver tumors in mice is also reduced (20,27). Furthermore, Zhang et al (28) revealed that colorectal cancer cell viability, colony formation, nude mice tumor growth, cell migration and invasion are repressed by miR-139, and Luo et al (29) demonstrated that proliferation, invasion and metastasis of laryngeal squamous carcinoma cells are also reduced. miR-139 functions as a tumor suppressor in esophageal squamous cell carcinoma by cell proliferation, migration and invasion inhibition, apoptosis induction and G0/G1 phase cell cycle arrest (22).…”

miR-139-5p controls translation in myeloid leukemia through EIF4G2

“…Accordingly, mir-139 is silenced in a number of solid tumors including hepatocellular carcinomas, gastric and metastatic breast cancers, laryngeal squamous cell carcinoma or glioma. 29,[38][39][40] Different mir-139 targets or pathways were proposed, which might explain the reduction of metastasis and tumor progression by mir-139, such as ROCK1, NOTCH1 (Notch-signaling), TCF4 (Wnt-pathway), CXCR4 or anti-apoptotic MCL1. 10,38,[41][42][43] Here, we described a mechanism, which might broadly explain the cell cycle inhibitory and pro-apoptotic effect of mir-139 in a wide range of neoplastic cells.…”

“…29,[38][39][40] Different mir-139 targets or pathways were proposed, which might explain the reduction of metastasis and tumor progression by mir-139, such as ROCK1, NOTCH1 (Notch-signaling), TCF4 (Wnt-pathway), CXCR4 or anti-apoptotic MCL1. 10,38,[41][42][43] Here, we described a mechanism, which might broadly explain the cell cycle inhibitory and pro-apoptotic effect of mir-139 in a wide range of neoplastic cells. By integrating proteomics data, global gene expression profiling and miRNA-target prediction algorithms, we show that mir-139 globally controls the cellular protein synthesis rate by targeting EIF4G2, an essential component of the translation initiation complex consisting of EIF4E, EIF4G and EIF4A.…”

Effect of EphA7 Silencing on Proliferation, Invasion and Apoptosis in Human Laryngeal Cancer Cell Lines Hep-2 and AMC-HN-8

“…Moreover, biomarkers are believed to be beneficial not only in evaluating the prognosis but also in guiding personalized therapy for patients with cancer [3,4]. Therefore, it is necessary to search for potential biomarkers of human LSCC.…”