title: miRNA-148a serves as a prognostic factor and suppresses migration and invasion through Wnt1 in non-small cell lung cancer.
abstract: Lung cancer is the leading cause of cancer death in the world, and aberrant expression of miRNA is a common feature during the cancer initiation and development. Our previous study showed that levels of miRNA-148a assessed by quantitative real-time polymerase chain reaction (qRT-PCR) were a good prognosis factor for non-small cell lung cancer (NSCLC) patients. In this study, we used high-throughput formalin-fixed and paraffin-embedded (FFPE) lung cancer tissue arrays and in situ hybridization (ISH) to determine the clinical significances of miRNA-148a and aimed to find novel target of miRNA-148a in lung cancer. Our results showed that there were 86 of 159 patients with low miRNA-148a expression and miRNA-148a was significantly down-regulated in primary cancer tissues when compared with their adjacent normal lung tissues. Low expression of miRNA-148a was strongly associated with high tumor grade, lymph node (LN) metastasis and a higher risk of tumor-related death in NSCLC. Lentivirus mediated overexpression of miRNA-148a inhibited migration and invasion of A549 and H1299 lung cancer cells. Furthermore, we validated Wnt1 as a direct target of miRNA-148a. Our data showed that the Wnt1 expression was negatively correlated with the expression of miRNA-148a in both primary cancer tissues and their corresponding adjacent normal lung tissues. In addition, overexpression of miRNA-148a inhibited Wnt1 protein expression in cancer cells. And knocking down of Wnt-1 by siRNA had the similar effect of miRNA-148a overexpression on cell migration and invasion in lung cancer cells. In conclusion, our results suggest that miRNA-148a inhibited cell migration and invasion through targeting Wnt1 and this might provide a new insight into the molecular mechanisms of lung cancer metastasis.
authors.affiliation: Department of Medical Oncology, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Departments of Respiratory Medicine, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China.
authors.forename: Lingfeng
authors.initials: L
authors.lastname: Min
authors.affiliation: Departments of Clinical Medical Testing Laboratory, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China.
authors.forename: Chuanli
authors.initials: C
authors.lastname: Ren
authors.affiliation: Departments of Respiratory Medicine, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China.
authors.forename: Xingxiang
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Medical Oncology, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China.
authors.forename: Jianqi
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Radiotherapy, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Xinchen
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Medical Oncology, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Departments of Respiratory Medicine, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China.
authors.forename: Changjiang
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Medical Oncology, Northern Jiangsu People's Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, China.
authors.forename: Xizhi
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000072283:A549 Cells; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000503:physiopathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D016086:Lentivirus / Q000235:genetics; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000503:physiopathology; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D034622:RNA Interference; D051155:Wnt1 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; C495247:WNT1 protein, human; D051155:Wnt1 Protein