Multidimensional communication of microRNAs and long non-coding RNAs in lung cancer

Abstract

Purpose: Non-coding RNAs (ncRNAs) have been a hot topic for many years in the field of cancer research, especially miRNAs and lncRNAs. Because they play critical roles in regulating various cellular processes and are more often involved in tumorigenesis than protein-coding genes. But the cross talk between miRNAs and lncRNAs in cancer has been scarcely studied. This article aims to provide a retrospective review of the latest research on the link between miRNAs and lncRNAs in lung cancer and discusses their potential role as diagnostic biomarkers and therapeutic targets for lung cancer in clinical practice.

Methods: We reviewed literatures about ncRNAs and lung cancer from PUBMED databases in this article.

Results: As shown in our review, miRNAs and lncRNAs could represent underlying targets for diagnosis, therapy, prognosis, and drug resistence of lung cancer. By acting as ceRNAs, lncRNAs can competitively inhibit the expression levels of miRNAs, and the lncRNA/miRNA axis can contribute to tumorigenesis, metastasis, and mutidrug resistance in lung cancer via various classic signaling pathways or related proteins.

Conclusion: Based on present knowledge, ncRNAs may provide a novel perspective to understand the pathogenesis of lung cancer and could be candidates in screening of therapeutic targets for lung cancer.

Keywords: EMT; Long non-coding RNAs; Lung cancer; Tumorigenesis; microRNAs.

Fig. 1

Biogenesis of miRNAs and lncRNAs that act as sponges for miRNAs. Both miRNAs and lncRNAs are transcribed by RNA polymerase II. miRNAs are derived from primary miRNAs several hundred nucleotides in length, which are cleaved and processed to become 20 and 25 nt-long miRNA duplexes. The resultant miRNAs are incorporated into the RNA-induced silencing complex (RISC), which targets mRNA and affects translational activities. lncRNAs interact directly with miRNAs to inhibit binding of miRNA to the 3′ UTR of target mRNA or indirectly by binding to the 3′ UTR of the target mRNA, which promotes degradation of the miRNA

Fig. 2

Classification of ncRNAs based on their genomic location. a Sense lncRNAs and overlapping sense lncRNAs located in the same strand as exons of protein-coding genes. b Antisense lncRNAs and overlapping antisense lncRNAs are transcribed in the opposite strand from protein-coding genes. c Bidirectional lncRNAs are initiated in a reverse fashion from the promoter of a neighboring protein-coding gene. d Intronic lncRNAs are initiated inside an intron of a protein-coding gene in either direction and terminate without overlapping exons. e Intergenic lncRNAs (also termed large intervening non-coding RNAs or linRNAs) behave as genomic interval units between two protein-coding genes

Fig. 3

Complex network between lncRNAs and miRNAs involved in ceRNA regulation in lung cancer. Regulation of the lncRNA/miRNA pathway in NSCLC can be classified into two main functional groups: tumor proliferation, invasion, metastasis, and apoptosis or chemotherapy resistance

Fig. 4

Regulatory network of several lncRNAs that function as sponges for miRNAs associated with epithelial–mesenchymal transition in the pathogenesis of lung cancer