shRNA‑mediated silencing of TARBP2 inhibits NCI‑H1299 non‑small cell lung cancer cell invasion and migration via the JNK/STAT3/AKT pathway.
Metastasis is a major cause of lung cancer-associated mortality. The current study aimed to investigate the effects and mechanisms of TAR (human immunodeficiency virus 1) RNA binding protein 2 (TARBP2) in the invasion and migration of non‑small cell lung cancer in vitro. The highly metastatic cell clone H1299/M02 was obtained by TARBP2 overexpression. Expression of TARBP2 in H1299/M02 was also downregulated to different levels via small hairpin RNAs (shRNAs). Subsequent to TARBP2 silencing, the proliferation of H1299/M02 cells was predominantly unaffected, while invasion and migration were significantly inhibited. A positive correlation was observed between invasion and migration and the level of TARBP2 silencing in vitro. Western blotting and reverse transcription‑quantitative polymerase chain reaction indicated that the protein expression levels of amyloid β (A4) precursor protein (APP) and zinc finger protein 395 (ZNF395) were upregulated, while expression levels of pro‑metastatic proteins including interleukin (IL)‑1β, IL‑8, cyclooxygenase (COX)‑2, matrix metalloproteinase 2 (MMP2) and MMP9 were downregulated. Phosphorylation of c‑Jun N‑terminal kinase (JNK), signal transducer and activator of transcription 3 (STAT3) and protein kinase B (AKT) were also inhibited. Overexpression of TARBP2 was suggested to be involved in the metastasis of H1299/M02 cells. Silencing of TARBP2 was able to upregulate levels of APP and ZNF395, in addition to inhibiting metastasis‑promoting cytokines, the JNK/STAT3/AKT pathway and COX‑2 to attenuate the invasion and migration of cancer cells.
Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer and Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China.
Yue
Y
Shi
Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer and Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China.
Duo
D
Zuo
Department of Gastrointestinal Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer and Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China.
Xia
X
Wang
Department of Clinical Laboratory, The First Center Hospital, Tianjin 300192, P.R. China.
Meng
M
Han
Department of Clinical Laboratory, TEAD Community Health Service Center, Tianjin 300457, P.R. China.
Yan
Y
Wu
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D008168:Lung / Q000473:pathology*; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D000099253:Trans-Activation Responsive RNA-Binding Protein
D048670:MAP Kinase Kinase 4; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D050796:STAT3 Transcription Factor; D000099253:Trans-Activation Responsive RNA-Binding Protein; C494086:STAT3 protein, human