Background: MicroRNAs (miRNAs) and Twist1-induced epithelial-mesenchymal transition (EMT) in cancer cell dissemination are well established, but the involvement of long noncoding RNAs (lncRNAs) in Twist1-mediated signaling remains largely unknown.Methods: RT-qPCR and western blotting were conducted to detect the expression levels of lncRNA JPX and Twist1 in lung cancer cell lines and tissues. The impact of JPX on Twist1 expression, cell growth, invasion, apoptosis, and in vivo tumor growth were investigated in lung cancer cells by western blotting, rescue experiments, colony formation assay, flow cytometry, and xenograft animal experiment.Results: We observed that lncRNA JPX was upregulated in lung cancer metastatic tissues and was closely correlated with tumor size and an advanced stage. Functionally, JPX promoted lung cancer cell proliferation in vitro and facilitated lung tumor growth in vivo. Additionally, JPX upregulated Twist1 by competitively sponging miR-33a-5p and subsequently induced EMT and lung cancer cell invasion. Interestingly, JPX and Twist1 were coordinately upregulated in lung cancer tissues and cells. Mechanically, the JPX/miR-33a-5p/Twist1 axis participated in EMT progression by activating Wnt/β-catenin signaling.Conclusions: These findings suggest that lncRNA JPX, a mediator of Twist1 signaling, could predispose lung cancer cells to metastasis and may serve as a potential target for targeted therapy.

The revolutionary findings in nonprotein-coding part of human genome analysis have revealed a large number of RNA transcripts longer than 200 nucleotides that lack coding protein function, termed long noncoding RNAs (lncRNAs). Recently, accumulating shreds of evidence suggest that lncRNAs are widely distributed in human genome and deeply involved in cellular activities such as cell growth, proliferation, and apoptosis. Generally, lncRNAs regulate cell behaviors by targeting cell cycle-associated cyclins, cyclin-dependent kinases (CDKs), and/or CDK inhibitors. Specifically, lncRNAs serve as scaffolds or guides for chromatin-modifying complexes and act as signals in response to DNA damage. In addition, lncRNAs function as protein decoys and microRNA decoys, as well as interveners in cell division by modulating oncogenes and/or tumor suppressors. In this review, we mainly focus on the current understanding of the molecular mechanisms, how lncRNAs influence cellular processes and cancer progression. Finally, we also prospect the limitations of lncRNAs in cell behaviors and the novel roles of lncRNAs in epigenetic regulations.

Cancer is characterized by multiple genetic and epigenetic alterations, including a higher prevalence of mutations of oncogenes and/or tumor suppressors. Mounting evidences have shown that noncoding RNAs (ncRNAs) are involved in the epigenetic regulation of cancer genes and their associated pathways. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9) system, a revolutionary genome-editing technology, has shed light on ncRNA-based cancer therapy. Here, we briefly introduce the classifications and mechanisms of CRISPR/Cas9 system. Importantly, we mainly focused on the applications of CRISPR/Cas9 system as a molecular tool for ncRNA (microRNA, long noncoding RNA and circular RNA, etc.) editing in human cancers, and the novel techniques that are based on CRISPR/Cas9 system. Additionally, the off-target effects and the corresponding solutions as well as the challenges toward CRISPR/Cas9 were also evaluated and discussed. Long- and short-ncRNAs have been employed as targets in precision oncology, and CRISPR/Cas9-mediated ncRNA editing may provide an excellent way to cure cancer.