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Review
. 2015 Jun 30;14:125.
doi: 10.1186/s12943-015-0402-5.

Aberrant Regulation of the LIN28A/LIN28B and let-7 Loop in Human Malignant Tumors and Its Effects on the Hallmarks of Cancer

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Free PMC article
Review

Aberrant Regulation of the LIN28A/LIN28B and let-7 Loop in Human Malignant Tumors and Its Effects on the Hallmarks of Cancer

Tianzhen Wang et al. Mol Cancer. .
Free PMC article

Abstract

RNA binding proteins (RBPs) and microRNAs (miRNAs) are two of the most important post-transcriptional regulators of gene expression, and their aberrant expression contributes to the development of human malignancies. Let-7, one of the most well-known tumor suppressors, is frequently down-regulated in a variety of human cancers. The RBP LIN28A/LIN28B, a direct target of the let-7 family of miRNAs, is an inhibitor of let-7 biogenesis and is frequently up-regulated in cancers. Aberrant regulation of the LIN28A/LIN28B and let-7 loop in human malignant tumors is reportedly involved in cancer development, contributing to cellular proliferation, cell death resistance, angiogenesis, metastasis, metabolism reprogramming, tumor-associated inflammation, genome instability, acquiring immortality and evading immune destruction. In this review, we summarized the mechanisms of LIN28A/LIN28B and let-7 loop aberrant regulation in human cancer and discussed the roles and potential mechanisms of the LIN28A/LIN28B and let-7 loop in regulating the hallmarks of cancer. The crosstalk between LIN28A/LIN28B and let-7 loop and certain oncogenes (such as MYC, RAS, PI3K/AKT, NF-κB and β-catenin) in regulating hallmarks of cancer has also been discussed.

Figures

Fig. 1
Fig. 1
A double-negative feedback loop between LIN28A/LIN28B and let-7
Fig. 2
Fig. 2
Let-7 targets insulin signaling pathway and thus inhibits cancer cell metabolism
Fig. 3
Fig. 3
A positive feedback between LIN28A/LIN28B and transcriptional factor NF-κB and STAT3 in the process of inflammation mediated cancer progression
Fig. 4
Fig. 4
The LIN28/let-7/MYC feedbacks loop and the crosstalk of hallmarks of cancer
Fig. 5
Fig. 5
Crosstalk between LIN28/let-7 loop and oncogenes in regulating hallmarks of cancer

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