DNMBP-AS1 Regulates NHLRC3 Expression by Sponging miR-93-5p/17-5p to Inhibit Colon Cancer Progression

Long non-coding RNAs (LncRNAs) act as competing endogenous RNAs (ceRNAs) in colon cancer (CC) progression, via binding microRNAs (miRNAs) to regulate the expression of corresponding messenger RNAs (mRNAs). This article aims to explore the detailed molecular mechanism of ceRNA in CC. Top mad 5000 lncRNAs and top mad 5000 mRNAs were used to perform weighted gene co-expression network analysis (WGCNA), and key modules were selected. We used 405 lncRNAs in the red module and 145 mRNAs in the purple module to build the original ceRNA network by online databases. The original ceRNA network included 50 target lncRNAs, 41 target miRNAs, and 34 target mRNAs. Fifty target lncRNAs were used to establish a prognostic risk model by univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. LncRNAs in the risk model were used to build the secondary ceRNA network, which contained 9 lncRNAs in the risk model, 35 miRNAs, and 29 mRNAs. Survival analyses of 29 mRNAs in the secondary ceRNA network have shown HOXA10 and NHLRC3 were identified as crucial prognostic factors. Finally, we constructed the last ceRNA network including 5 lncRNAs in the risk model, 8 miRNAs, and 2 mRNAs related to prognosis. Quantitative real-time polymerase chain reaction (qRT-PCR) results revealed that DNMBP-AS1 and FAM87A were down-regulated in CC cells and tissues. Function assays showed that over-expression of DNMBP-AS1 and FAM87A inhibited CC cells proliferation and migration. Mechanism study showed that DNMBP-AS1 served as miR-93-5p/17-5p sponges and relieved the suppression effect of miR-93-5p/17-5p on their target NHLRC3. Our study suggested that DNMBP-AS1 inhibited the progression of colon cancer through the miR-93-5p/17-5p/NHLRC3 axis, which could be potential therapeutic targets for CC.

Automated summary

This study explores the molecular mechanism of long non-coding RNAs as competing endogenous RNAs in colon cancer. By constructing ceRNA networks and a prognostic risk model, this study identifies DNMBP-AS1 as a potential therapeutic target for colon cancer progression through the miR-93-5p/17-5p/NHLRC3 axis.