Targeting H19 by lentivirus-mediated RNA interference increases A549 cell migration and invasion.
Lung cancer is one of the most common and a lethal malignancy in the world and non-small cell lung cancer (NSCLC) is the most usual type. H19 long non-coding RNA (lncRNA) plays essential roles in tumor development. But its role in tumor metastasis is still unclear.



MACC1 RNAi and Lentivirus-mediated H19-specific shRNA was used to establish H19 stable knocking-down A549 cells. Transwell assays were performed to examine the effect of H19 knocking-down on A549 cells migration and invasion. The downstream signaling proteins targeted by H19 were also examined by western blot. AG1478 and U0126 were used as the inhibitor of EGFR and ERK1/2, respectively.



The knockdown of H19 increased the migration and invasion of A549 cells, and knockdown of metastasis-associated in colon cancer 1 (MACC1) decreased the migration and invasion of A549 cells. Furthermore, MACC1 protein targeted by H19 was upregulated as well as the downstream signaling proteins including epidermal growth factor receptor (EGFR), β-catenin, extracellular-signal-regulated kinase 1/2 (ERK1/2). Inhibited the expression of EGFR or ERK1/2 significantly decreased the migration and invasion of tumor cells.



Our findings showed that H19 functions as a suppressor of NSCLC and plays an important role in the migration and invasion of NSCLC. More importantly, H19 may regulate NSCLC metastasis through modulating cellular signaling pathway proteins related to cell proliferation and cell adhesion, including MACC1, EGFR, β-catenin and ERK1/2. These results put forward our understanding of the detailed mechanism of H19 lncRNA regulating the process of NSCLC metastasis.
a Department of Oncology , Guangzhou Red Cross Hospital, Medical College, Jinan University , Guangzhou , China.
Lin
L
Wang
b Department of Gastroenterology , The Third Affiliated Hospital of Guangzhou Medical University , Guangzhou , China.
Yan
Y
Sun
a Department of Oncology , Guangzhou Red Cross Hospital, Medical College, Jinan University , Guangzhou , China.
Jiqun
J
Yi
a Department of Oncology , Guangzhou Red Cross Hospital, Medical College, Jinan University , Guangzhou , China.
Xiuwen
X
Wang
a Department of Oncology , Guangzhou Red Cross Hospital, Medical College, Jinan University , Guangzhou , China.
Jizhen
J
Liang
a Department of Oncology , Guangzhou Red Cross Hospital, Medical College, Jinan University , Guangzhou , China.
Zhaojun
Z
Pan
a Department of Oncology , Guangzhou Red Cross Hospital, Medical College, Jinan University , Guangzhou , China.
Li
L
Li
c Central Laboratory, Tianyou Hospital, Wuhan University of Science and Technology , Wuhan , China.
Gaofeng
G
Jiang
D000072283:A549 Cells; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D006801:Humans; D016086:Lentivirus; D008175:Lung Neoplasms / Q000473:pathology*; D020935:MAP Kinase Signaling System; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000494:pharmacology*; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
C495270:CTNNB1 protein, human; C094335:H19 long non-coding RNA; C544162:MACC1 protein, human; D062085:RNA, Long Noncoding; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin
H19; cell invasion; cell migration; epidermal growth factor receptor; extracellular-signal-regulated kinase 1/2; lung cancer; metastasis-associated in colon cancer 1; non-small cell lung cancer; β-catenin