Theoretical perspectives and clinical applications of non-coding RNA in lung cancer metastasis: a systematic review

Abstract

Lung cancer is one of the deadliest malignancies worldwide, with distant metastasis being a major cause of death. However, the specific mechanisms of lung cancer metastasis remain unclear. NcRNAs, a widely present type of non-coding RNAs in the body, constitute about 98% of the human genome, lacking protein-coding capacity but involved in various cellular processes such as proliferation, apoptosis, invasion, and migration. Studies have shown that ncRNAs play a crucial role in the metastasis of lung cancer, although research in this area is limited. This review summarizes the biological origins and functions of ncRNAs, their specific roles and mechanisms in lung cancer metastasis, and discusses their potential for early screening and therapeutic applications in lung cancer. Furthermore, it outlines the challenges in translating basic advancements of ncRNAs in lung cancer metastasis into clinical practice.

Keywords: Circular RNA; Long non-coding RNA; Lung cancer; Metastasis; MicroRNA; Non-coding RNA.

Fig. 1

Mechanism of Lung Cancer Metastasis. Tumors induce angiogenesis through tumor-associated macrophages and various vasoactive factors. Additionally, tumors can recruit endothelial progenitor cells to induce angiogenesis. Due to the lack of tight cell junctions between lymphatic endothelial cells, lymphatic vessels are more permeable than blood vessels. After invading the circulation, cancer cells preferentially bind to platelets. The interaction between platelets and cancer cells facilitates their extravasation into target tissues, where they colonize and thrive in the microenvironment that supports their growth

Fig. 2

Biogenesis and Functional Effects of ncRNAs. DNA nucleotides are transcribed into primary miRNA transcripts by RNA polymerase II. These are then processed into precursor miRNA within the nucleus. Subsequently, pre-miRNAs are transported to the cytoplasm via exportin-5 and RAN-GTP. In the cytoplasm, they are further processed by the DICER endonuclease into mature miRNAs, which then return to the nucleus to exert their functions. lncRNAs are transcribed by RNA polymerase II from promoter regions of independent genes, producing intronic lncRNA, intergenic lncRNA (lincRNA), and natural antisense transcripts. These lncRNAs exit the nucleus to act as competing endogenous RNAs or interact with proteins. circRNAs are produced by back-splicing of pre-mRNA, forming a closed loop by covalently linking the 5’-head to the 3’-tail. circRNAs can also function as ceRNAs or interact with proteins