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

通过在竞争内源 RNA 网络上随机行走来识别与肺腺癌相关的长链非编码 RNA

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作者: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.

Conclusions

In brief, the lncRNAs were predicted to serve as potential biomarkers for the diagnosis, treatment, and prognosis of LUAD.

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.

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