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Review
. 2017 Apr 11;8(15):25721-25735.
doi: 10.18632/oncotarget.14891.

Oncogenic mechanisms of Lin28 in breast cancer: new functions and therapeutic opportunities

Hanchu Xiong  1   2 , Wenhe Zhao  1   2 , Ji Wang  1   2 , Benjamin J Seifer  3 , Chenyang Ye  4 , Yongxia Chen  1   2 , Yunlu Jia  1   2 , Cong Chen  1   2 , Jianguo Shen  1   2 , Linbo Wang  1   2 , Xinbing Sui  2   5 , Jichun Zhou  1   2
Affiliations
Review

Oncogenic mechanisms of Lin28 in breast cancer: new functions and therapeutic opportunities

Hanchu Xiong et al. Oncotarget. .

Abstract

The RNA binding protein Lin28 is best known for the critical role in cell development, recent researches also have implied its oncogenic function in various human cancers, including breast cancer. Specifically, aberrant Lin28 participates in multiple pathological processes, such as proliferation, metastasis, radiotherapy and chemotherapy resistance, metabolism, immunity and inflammation as well as stemness. In this review, we summarize the let-7-dependent and let-7-independent mechanism regulated by Lin28, focusing on its relation with tumor hallmarks in breast cancer, and subsequently discuss our present knowledge of Lin28 to develop a molecular-based therapeutic strategy against breast cancer.

Keywords: Let-7; Lin28; breast cancer; drug resistance; metastasis.

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Conflict of interest statement

CONFLICTS OF INTEREST

No potential conflicts of interest were disclosed. None of the contents of this manuscript has been previously published or is under consideration elsewhere. All the authors read and approved the final version of the manuscript prior to submission.

Figures

Figure 1
Figure 1. Domains of human Lin28A and Lin28B proteins
Lin28A and Lin28B share several common domains: the CSD (yellow) and CCHC (orange), while Lin28B contains both NoLS and NLS (gray). Numbers denote amino acids.
Figure 2
Figure 2. Lin28′s let-7-dependent functionality
A primary let-7 (pri-let-7) transcript produced by let-7 gene is processed by the Drosha DGCR8 microprocessor in the nucleus. Then the generated precursor let-7 (pre-let-7) is transported to the cytosol and further processed by the Dicer and Argonaute proteins (AGO) to generate the mature let-7. The biogenesis of pri-let-7 is blocked by Lin28A in the nucleus and Lin28B in the nucleolus, the biogenesis of pre-let-7 and mature let-7 are blocked by Lin28A/B in the cytosol, and the mature let-7 can in turn block the biogenesis of Lin28A/B. Solid line arrows refer to induction and promotion, dash line arrows refer to only promotion, while hammerheads refer to inhibition.
Figure 3
Figure 3. Lin28′s let-7-independent functionality
Lin28 can regulate multiple tumor-associated progressions without let-7, but with proliferation (CyclinA/B/D, CDK1/2/4/6, miR-125b), chemoresistance (pRb, p21, Bcl-xL, miR-107), metabolism (IGF2, Oxidative enzymes), inflammation (hnRNP A1), stemness (OCT4, miR-200), cell development (Hbl-1, Lin4/14, miR-48/84/241) related proteins and RNAs. Arrows refer to promotion, while hammerheads refer to inhibition.
Figure 4
Figure 4. Lin28 regulates multiple progressions in breast cancer
Lin28 exerts its critical role in breast cancer through two distinct ways: let-7 dependent and let-7 independent. Orange refers to factors of let-7-dependent way, blue refers to factors of let-7-independent way, gray means factors involved in both mechanisms.
See this image and copyright information in PMC

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