BackgroundThe efficacy of cisplatin-based chemotherapy in non-small-cell lung cancer is limited by the acquired drug resistance. Identification the RNAs related to the cisplatin resistance may help to improve clinical response rates.MethodsMicroarray expression profiling of mRNAs, lncRNA and miRNA was undertaken in A549 cells and cisplatin resistant A549/CDDP cells. Differentially expressed mRNAs, lncRNAs and miRNAs, verified by realtime RT-PCR, were subjected to pathway analysis. Expression of NKD2 and β-catenin was assessed by realtime RT-PCR and western blot analysis. The effect of lncRNA AK126698 on cisplatin induced apoptosis was investigated by annexin-V/PI flow cytometry.ResultsIn total, 1471 mRNAs, 1380 lncRNAs and 25 miRNAs differentially expressed in A549/CDDP and A549 cells. Among them, 8 mRNAs, 8 lncRNAs and 5 miRNAs differentially expressed in gene chip analysis were validated. High-enrichment pathway analysis identified that some classical pathways participated in proliferation, differentiation, avoidance of apoptosis, and drug metabolism were differently expressed in these cells lines. Gene co-expression network identified many genes like FN1, CTSB, EGFR, and NKD2; lncRNAs including BX648420, ENST00000366408, and AK126698; and miRNAs such as miR-26a and let-7i potentially played a key role in cisplatin resistance. Among which, the canonical Wnt pathway was investigated because it was demonstrated to be targeted by both lncRNAs and miRNAs including lncRNA AK126698. Knockdown lncRNA AK126698 not only greatly decreased NKD2 which can negatively regulate Wnt/β-catenin signaling but also increased the accumulation and nuclear translocation of β-catenin, and significantly depressed apoptosis rate induced by cisplatin in A549 cells.ConclusionCisplatin resistance in non-small-cell lung cancer cells may relate to the changes in noncoding RNAs. Among these, AK126698 appears to confer cisplatin resistance by targeting the Wnt pathway.

BackgroundCircular RNA (circRNA) is a novel class of noncoding RNAs with functions in various pathophysiological activities. However, the expression profiles and functions of circRNAs in colorectal cancer (CRC) remain largely unknown.MethodsHigh-throughput RNA sequencing (RNA-seq) was performed to assess circRNA expression profiles in 4 paired CRC tissues, and significantly dysregulated circRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict the potential functions of dysregulated circRNAs. Target miRNAs of circRNAs were predicted using miRanda software, and were further analyzed combining DIANA-miRPath v.3 platform (Reverse Search module) with KEGG pathways of COLORECTAL CANCER and MicroRNAs in cancer (Entry: map05210 and map05206). CircRNA-miRNA interaction networks were constructed using Cytoscape software. Expression levels of a significantly down-regulated circRNA, circDDX17 (hsa_circ_0002211), was detected by qRT-PCR in 60 paired CRC tissues. CircDDX17 was knockdown by siRNA, and the biological functions of circDDX17 were examined in CRC cell lines.ResultsTotally 448 differentially expressed circRNAs were identified, including 394 up-regulated and 54 down-regulated circRNAs. qRT-PCR validation confirmed the reliability of the RNA-Seq data. GO and KEGG analyses revealed that these dysregulated circRNAs were potentially implicated in CRC pathogenesis. Analyses by combining miRanda and miRPath softwares with KEGG pathways suggested that the miRNAs targeted by the top 10 dysregulated circRNAs were associated with the KEGG pathways of COLORECTAL CANCER and MicroRNAs in cancer, indicating that circRNA-miRNA interactions might play important functional roles in the initiation and progression of CRC. The results of qRT-PCR for circDDX17 in 60 paired CRC tissues showed that circDDX17 was significantly down-regulated in CRC tissues and associated with unfavorable clinicopathological parameters. In vitro experiments showed that silencing of circDDX17 promoted CRC cell proliferation, migration, invasion, and inhibited apoptosis.ConclusionsIn conclusion, we have identified numerous circRNAs that are dysregulated in CRC tissues compared with adjacent normal mucosa tissues. Bioinformatic analyses suggested that these dysregulated circRNAs might play important functional roles in CRC tumorigenesis. CircDDX17 functions as a tumor suppressor and could serve as a potential biomarker and a therapeutic target for CRC.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-1006-x) contains supplementary material, which is available to authorized users.

No abstract