Identification of lung-adenocarcinoma-related long non-coding RNAs by random walking on a competing endogenous RNA network

Hongyan Zhang, Yuan Wang, Jibin Lu


Background: Identification of novel risk long non-coding RNAs (lncRNAs) in lung adenocarcinoma (LUAD) is still a significant challenge in cancer research.
Methods: In this study, we first constructed a LUAD-specific competing endogenous RNA (ceRNA) network using both experimental- and computational-supported datasets. Then, a random walking with restart method was performed to predict LUAD-associated risk lncRNAs based on the ceRNA network. The role of lncRNA MAPKAPK5-AS1 was assessed by siRNA transfection, followed by a colony formation assay, the CCK-8 assay, and immunofluorescence on A549 cells.
Results: Our method achieved an area under the curve (AUC) value of over 0.83. Of the several potential novel LUAD-related lncRNAs identified, the highest ranked lncRNA was SNHG12, which, interestingly, was also shown to promote tumorigenesis and metastasis in LUAD in a recent study. Furthermore, we found that the expression of MAPKAPK5-AS1, which was ranked second, was higher in both LUAD tissues and three LUAD cell lines. After the silencing of MAPKAPK5-AS1 by siRNA transfection, a colony formation assay revealed fewer colonies, and a CCK-8 assay revealed significantly suppressed growth of A549 cells. Moreover, immunofluorescence staining of Ki-67, a proliferation marker, revealed that the proliferation capability of A549 was dramatically reduced following MAPKAPK5-AS1 downregulation. AO/EB staining showed an increased proportion of apoptotic cells among A549 cells depleted of MAPKAPK5-AS1.
Conclusions: In brief, the lncRNAs were predicted to serve as potential biomarkers for the diagnosis, treatment, and prognosis of LUAD.