AUTHOR=Xu Zhenglei , Zhang Dingguo , Zhang Zhuliang , Luo Weixiang , Shi Ruiyue , Yao Jun , Li Defeng , Wang Lisheng , Liao Bihong
TITLE=MicroRNA-505, Suppressed by Oncogenic Long Non-coding RNA LINC01448, Acts as a Novel Suppressor of Glycolysis and Tumor Progression Through Inhibiting HK2 Expression in Pancreatic Cancer
JOURNAL=Frontiers in Cell and Developmental Biology
VOLUME=8
YEAR=2021
URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.625056
DOI=10.3389/fcell.2020.625056
ISSN=2296-634X
ABSTRACT=
Background: MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) play vital regulatory roles in pancreatic cancer (PC) initiation and progression. We aimed to explore the biological functions and underlying mechanisms of miR-505-3p (miR-505) in PC.
Methods: We first screened miRNA expression profiles using microarray in PC tissues and normal tissues, and then studied the function and underlying mechanism of miR-505. Moreover, we evaluated the regulatory effect of lncRNA LINC01448 on miR-505.
Results: We demonstrated miR-505 that was significantly downregulated in PC tissues. We further revealed that miR-505 significantly inhibited cell proliferation, invasion, sphere formation, glucose consumption, and lactate production by targeting HK2. In addition, overexpression of miR-505 led to tumor growth inhibition in vivo, demonstrating that it acts as a tumor suppressor in PC. LINC01448 was identified as an oncogenic lncRNA that could reduce miR-505 expression. Subsequent studies confirmed that LINC01448 enhanced cell proliferation, invasion, sphere formation, glucose consumption, and lactate production by regulating the miR-505/HK2 pathway.
Conclusions: These findings demonstrated that miR-505, suppressed by LINC01448, could function as a key tumor suppressor by targeting HK2 in PC, elucidating an important role of the LINC01448/miR-505/HK2 pathway in regulating PC glycolysis and progression.