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World J Biol Chem. Mar 27, 2022; 13(2): 35-46
Published online Mar 27, 2022. doi: 10.4331/wjbc.v13.i2.35
LIN28A: A multifunctional versatile molecule with future therapeutic potential
Kenneth Wu, Tauseef Ahmad, Rajaraman Eri
Kenneth Wu, Tauseef Ahmad, Rajaraman Eri, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Tasmania 7250, Australia
Author contributions: Wu K wrote the review; all authors have read and approved the final version of the review.
Conflict-of-interest statement: The authors declare no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Rajaraman Eri, DVM, PhD, Associate Professor, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Health Sciences Building (Newnham-C), 2nd Level, Room M216, Launceston, Tasmania 7250, Australia.
Received: March 27, 2021
Peer-review started: March 27, 2021
First decision: July 27, 2021
Revised: September 6, 2021
Accepted: March 4, 2022
Article in press: March 4, 2022
Published online: March 27, 2022

An RNA-binding protein, LIN28A was initially discovered in nematodes Caenorhabditis elegans and regulated stem cell differentiation and proliferation. With the aid of mouse models and cancer stem cells models, LIN28A demonstrated a similar role in mammalian stem cells. Subsequent studies revealed LIN28A’s roles in regulating cell cycle and growth, tissue repair, and metabolism, especially glucose metabolism. Through regulation by pluripotency and neurotrophic factors, LIN28A performs these roles through let-7 dependent (binding to let-7) or independent (binding directly to mature mRNA) pathways. Elevated LIN28A levels are associated with cancers such as breast, colon, and ovarian cancers. Overexpressed LIN28A has been implicated in liver diseases and Rett syndrome whereas loss of LIN28A was linked to Parkinson’s disease. LIN28A inhibitors, LIN28A-specific nanobodies, and deubiquitinases targeting LIN28A could be feasible options for cancer treatments while drugs upregulating LIN28A could be used in regenerative therapy for neuropathies. We will review the upstream and downstream signalling pathways of LIN28A and its physiological functions. Then, we will examine current research and gaps in research regarding its mechanisms in conditions such as cancers, liver diseases, and neurological diseases. We will also look at the therapeutic potential of LIN28A in RNA-targeted therapies including small interfering RNAs and RNA-protein interactions.

Keywords: Let-7, Differentiation, Proliferation, Cancer, Inflammation

Core Tip: The overexpression of LIN28A has been correlated with a number of tumours and a higher risk of relapse in cancer patients. Therefore, LIN28A could be developed as a prognostic indicator. With an increasing understanding of its roles in the pathological context, LIN28A has also become a promising therapeutic target for cancer treatment and regenerative therapy for neuropathies.