miR-206/133b Cluster: A Weapon against Lung Cancer?

Abstract

Lung cancer is a deadly disease that ends numerous lives around the world. MicroRNAs (miRNAs) are a group of non-coding RNAs involved in a variety of biological processes, such as cell growth, organ development, and tumorigenesis. The miR-206/133b cluster is located on the human chromosome 6p12.2, which is essential for growth and rebuilding of skeletal muscle. The miR-206/133b cluster has been verified to be dysregulated and plays a crucial role in lung cancer. miR-206 and miR-133b participate in lung tumor cell apoptosis, proliferation, migration, invasion, angiogenesis, drug resistance, and cancer treatment. The mechanisms are sophisticated, involving various target genes and molecular pathways, such as MET, EGFR, and the STAT3/HIF-1α/VEGF signal pathway. Hence, in this review, we summarize the role and potential mechanisms of the miR-206/133b cluster in lung cancer.

Keywords: lung cancer; miR-133b; miR-206; miR-206/133b cluster.

Figure 1

miR-133b/206 Associates with Various Genes Mediating NSCLC Cell Migration and Invasion miR-206 promoted lung cancer cell apoptosis by targeting c-Met and Bcl2, as well as governed EGFR, MET, and its downstream phosphorylation of ERK1/2 and AKT. Likewise, miR-133b boosted lung cancer cell apoptosis by suppressing expression of MCL1, BCL2L2, and attenuated EGFR and its downstream phosphorylation of ERK1/2 and AKT. Furthermore, miR-206 inhibited lung cancer cell migration and invasion by repressing SOX9 and Smad3 and upregulating E-cadherin, meanwhile blocked EGFR, MET, and its downstream phosphorylation of ERK1/2 and AKT, as well as antagonized c-Met and the PI3K/Akt/mTOR pathway. miR-133b repressed FSCN1, contributing to the blockage of lung cancer cell migration and invasion.

Figure 2

miR-206 Associates with Various Genes Mediating NSCLC Cell Proliferation NRF2 could decrease miR-206 expression, while miR-206 was able to repress the pentose phosphate pathway genes (G6PD, PGD, TKT, and GPD2), reducing pentose phosphate pathway-related NADPH production and ribose synthesis and then giving rise to blockage of lung cancer cell proliferation. In addition, TGF-β1 enabled miR-206 to decline, whereas restoration of miR-206 significantly suppressed the level of Samd3 and TRIB2, leading to inhibit proliferation. However, miR-206 also directly repressed Bcl2 and c-Met expression, contributing to inhibition of cell proliferation in lung cancer.