UCA1 Regulates the Growth and Metastasis of Pancreatic Cancer by Sponging miR-135a.
Pancreatic cancer (PC) is a devastating malignant disease with a poor prognosis. This study aimed to investigate the role of urothelial carcinoma associated 1 (UCA1) in the progression of PC. Our results revealed that long noncoding RNA (lncRNA) UCA1 was overexpressed in PC tissues compared with adjacent histologically normal tissues. A downregulated level of UCA1 was also detected in five human PC cell lines (SW1990, BxPC-3, MiaPaCa-2, PANC-1, and CAPAN-1) compared with normal pancreatic duct epithelial HPDE cells. The proliferation of PC cells was inhibited after UCA1 was suppressed by a lentiviral vector. The cell apoptosis rate was largely promoted by downregulating UCA1. Further research revealed that microRNA (miRNA)-135a is a direct target of UCA1. The expression of miR-135a was decreased in PC tissues and cell lines compared with control groups. In addition, the decreased level of miR-135a was elevated by adding miR-135a mimic in SW1990 cells transfected with lncRNA UCA1. Similarly, an upregulated level of miR-135a was downregulated by adding miR-135a inhibitor in SW1990 cells transfected with UCA1 siRNA. Luciferase activity assay further confirmed the targeting relationship between UCA1 and miR-135a. Moreover, miR-135a reversed the effect of UCA1 on cell apoptosis rate and cell viability in SW1990 cells. The migration and invasion capacities of PC cells were suppressed by UCA1. siRNA was then enhanced by the miR-135a inhibitor. In vivo, UCA1 siRNA effectively suppressed tumor growth and the expression of migration markers. Taken together, our research revealed that UCA1 works as an oncogene by targeting miR-135a. The UCA1-miR-135a pathway regulated the growth and metastasis of PC, providing new insight in the treatment of PC.
Xiaobo
X
Zhang
Feng
F
Gao
Lei
L
Zhou
Huaitao
H
Wang
Gang
G
Shi
Xiaodong
X
Tan
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D062085:RNA, Long Noncoding / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
C544965:MIRN135 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; C515159:UCA1 RNA, human