Role of circular RNAs in the diagnosis, regulation of drug resistance and prognosis of lung cancer

Abstract

Lung cancer is one of the most common malignant tumors in China and is the highest cause of mortality among male and female patients, both in urban and rural areas. A subset of patients with lung cancer only display chest tightness without any other obvious symptoms. This is because most symptoms do not manifest during the early stages of disease development. Consequently, most patients with lung cancer are diagnosed when the disease is in the advanced stages, when they are already unfit for surgical treatment. Furthermore, the prognosis of patients with lung cancer is poor. The 5-year survival rate of patients with stage IA lung cancer is 85%, compared with 6% in those with stage IV. This requires the development of strategies for early diagnosis, treatment and prognosis to improve the management of lung cancer. Circular RNAs (circRNAs) belong to a class of closed circular non-coding RNAs formed by reverse splicing of a precursor mRNA. These RNAs are highly stable, ubiquitously expressed, conserved, and show high specificity. CircRNAs regulate biological processes, such as the proliferation, differentiation and invasion of lung cancer cells. Therefore, they can be used as biomarkers for the early diagnosis and prognosis prediction of lung cancer, as well as novel targets for therapy design. In the present review, the biological characteristics and functions of circRNAs, as well as their application in the diagnosis, control of drug resistance and effect on the prognosis of patients with lung cancer, will be discussed.

Keywords: circular RNAs; diagnosis; drug resistance; lung cancer; prognosis.

Figure 1.

Loop formation mechanism of circRNAs. (A) ciRNA. (B) Lasso-driven cyclization. (C) Intron pairing-driven cyclization. (D) RBP-driven cyclization. CircRNA, circular RNA; ciRNA, intron circRNA; EcircRNAs, exon circRNAs; EIciRNAs, exon intron circRNAs; RBP, RNA binding protein.

Figure 2.

Biological functions of circRNAs. (A) Regulation of the transcription of parental genes. (B) Function as miRNA ‘sponge’. (C) Interaction with RBPs. (D) Protein translation. CircRNA, circular RNA; Pol II, RNA polymerase II; snRNA, small nuclear RNA; EcircRNAs, exon circRNAs; miRNA, microRNA; RBP, RNA binding protein.

Figure 3.

CircRNAs and adjuvant therapy resistance in lung cancer. The circRNAs are mainly divided into four aspects: CircRNAs related to drug resistance in chemotherapy of lung cancer, circRNAs related to drug resistance in targeted therapy of lung cancer, circRNAs related to drug resistance in immunotherapy of lung cancer and circRNAs related to drug resistance in radiotherapy of lung cancer. Circ, circular.

Figure 4.

Association of circRNAs with clinicopathological features of patients with lung cancer. The percentage values shown on the Y-axis refer to the proportion of studies on circRNAs in the 20 lung cancer cases presented in the table. ‘Statistically significant’ and ‘No statistical significance’ refers to the associations between circRNA levels and the clinical features, while ‘Not included in the study’ refers to clinical features that have not been used as indicators of circRNAs.