PMID- 27533461 OWN - NLM STAT- MEDLINE DCOM- 20180223 LR - 20211209 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 7 IP - 36 DP - 2016 Sep 6 TI - MicroRNA 744-3p promotes MMP-9-mediated metastasis by simultaneously suppressing PDCD4 and PTEN in laryngeal squamous cell carcinoma. PG - 58218-58233 LID - 10.18632/oncotarget.11280 [doi] AB - MicroRNA controls cancer invasion by governing the expression of gene regulating migration and invasion. Here, we reported a novel regulatory pathway controlled by miR-744-3p, which enhanced expression of matrix metallopeptidase 9 (MMP-9) in laryngeal squamous cell carcinoma (LSCC). We profiled the differential micoRNA expression pattern in LSCC cell lines and normal epithelial cultures derived from the head and neck mucosa using microRNA microarray. MiR-7-1-3p, miR-196a/b and miR-744-3p were expressed differentially in the LSCC cell lines. Subsequent validation using real-time PCR revealed that high miR-744-3p level was positively correlated with regional lymph node metastasis of LSCC. Real-time cellular kinetic analysis showed that suppressing miR-744-3p could inhibit migration and invasion of LSCC cell lines and reduce the number of lung metastatic nodules in nude mice modules. In silico analysis revealed that miR-744-3p targeted 2 distinct signaling cascades which eventually upregulated MMP-9 expression in LSCC. First, miR-744-3p could suppress programmed cell death 4 (PDCD4), a direct suppressor of NF-kappaB (p65). PDCD4 could also prevent AKT activation and suppress MMP-9 expression. Further, suppressing miR-744-3p expression could restore phosphatase and tensin homolog (PTEN) expression. PTEN could inhibit AKT activation and inhibit MMP-9 expression in LSCC cells. The results revealed that suppressing miR-744-3p was effective to inhibit LSCC metastasis by inactivating AKT/mTOR and NF-kappaB (p65) signaling cascade. Targeting miR-744-3p could be a valuable therapeutic intervention to suppress the aggressiveness of LSCC. FAU - Li, John Zeng-Hong AU - Li JZ AD - Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong. AD - Department of Otolaryngology, The First People's Hospital of Foshan, Foshan, People's Republic of China. FAU - Gao, Wei AU - Gao W AD - Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong. FAU - Lei, Wen-Bin AU - Lei WB AD - Department of Otolaryngology, The First Affiliated Hospital of Sun Yet-Sen University, Guangdong, People's Republic of China. FAU - Zhao, Jing AU - Zhao J AD - Department of Otolaryngology, The First Affiliated Hospital of Sun Yet-Sen University, Guangdong, People's Republic of China. FAU - Chan, Jimmy Yu-Wai AU - Chan JY AD - Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong. FAU - Wei, William Ignace AU - Wei WI AD - Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong. FAU - Ho, Wei-Kuen AU - Ho WK AD - Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong. FAU - Wong, Thian-Sze AU - Wong TS AD - Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Hong Kong. LA - eng PT - Journal Article PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (MIRN744 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (PDCD4 protein, human) RN - 0 (RELA protein, human) RN - 0 (RNA, Small Interfering) RN - 0 (RNA-Binding Proteins) RN - 0 (Transcription Factor RelA) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) RN - EC 3.1.3.67 (PTEN protein, human) RN - EC 3.4.24.35 (MMP9 protein, human) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Animals MH - Apoptosis Regulatory Proteins/*genetics/metabolism MH - Carcinoma, Squamous Cell/*genetics/pathology/secondary MH - Cell Line, Tumor MH - *Gene Expression Regulation, Neoplastic MH - Head and Neck Neoplasms/*genetics/pathology/secondary MH - Humans MH - Laryngeal Neoplasms/*genetics/pathology MH - Larynx/pathology MH - Lung/pathology MH - Lung Neoplasms/*genetics/pathology/secondary MH - Lymphatic Metastasis MH - Matrix Metalloproteinase 9/*metabolism MH - Mice MH - Mice, Nude MH - MicroRNAs/genetics/*metabolism MH - Middle Aged MH - Neoplasm Staging MH - Oncogenes MH - PTEN Phosphohydrolase/*genetics/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - RNA Interference MH - RNA, Small Interfering/metabolism MH - RNA-Binding Proteins/*genetics/metabolism MH - Real-Time Polymerase Chain Reaction MH - Signal Transduction/genetics MH - Squamous Cell Carcinoma of Head and Neck MH - TOR Serine-Threonine Kinases/metabolism MH - Transcription Factor RelA/metabolism MH - Xenograft Model Antitumor Assays PMC - PMC5295426 OTO - NOTNLM OT - PDCD4 OT - PTEN OT - laryngeal squamous cell carcinoma OT - metastasis OT - miR-744-3p COIS- No conflicts of interest were declared. EDAT- 2016/08/18 06:00 MHDA- 2018/02/24 06:00 PMCR- 2016/09/06 CRDT- 2016/08/18 06:00 PHST- 2015/09/22 00:00 [received] PHST- 2016/08/08 00:00 [accepted] PHST- 2016/08/18 06:00 [pubmed] PHST- 2018/02/24 06:00 [medline] PHST- 2016/08/18 06:00 [entrez] PHST- 2016/09/06 00:00 [pmc-release] AID - 11280 [pii] AID - 10.18632/oncotarget.11280 [doi] PST - ppublish SO - Oncotarget. 2016 Sep 6;7(36):58218-58233. doi: 10.18632/oncotarget.11280.