miR-28: A Tiny Player in Cancer Progression and Other Human Diseases

Abstract

MicroRNAs belong to a class of small non-coding RNA molecules that regulate gene expression post-transcriptionally. By binding to specific mRNA sequences, microRNAs can either inhibit translation or promote transcript degradation. MicroRNA-28 (miR-28) plays a pivotal role in regulating the processes responsible for the pathogenesis of numerous diseases. Its function is contingent upon the specific type of disease and the cellular microenvironment. miR-28 can act as both an inhibitor and inducer of pathogenic processes. This article discusses the impact of miR-28 on the progression of various types of cancer, with particular emphasis on its role as a regulator of gene expression involved in cell proliferation, apoptosis, invasion, migration, and metastasis. Additionally, the article delves into the role of miR-28 in other human diseases and its influence on the processes that underlie their development. A comprehensive understanding of the precise mechanisms through which this specific microRNA exerts its regulatory functions could significantly impact the development of novel therapies. Furthermore, there is potential for miR-28 to be utilized as a diagnostic and preventative biomarker.

Keywords: biomarker; cancer; circRNA; lncRNA; metastasis; miR-28; miRNA; non-coding RNA; oncogene; oncomiR.

Figure 1

Scheme of miRNA biogenesis and its role in gene expression regulation. miRNA is transcribed from DNA by RNA polymerase II into primary miRNA (pri-miRNA). The pri-miRNA is then processed by the microprocessor complex, including Drosha, into precursor miRNAs (pre-miRNAs). Pre-miRNAs are subsequently exported from the nucleus to the cytoplasm via Exportin-5. In the cytoplasm, the pre-miRNA is cleaved by the Dicer enzyme, generating a double-stranded miRNA. The miRNA duplex binds to the RNA-induced silencing complex (RISC), where the Argonaute protein is the active part necessary for preventing protein production. The mature strand remains in RISC and binds to target mRNA for gene regulation, while the passenger strand is degraded. Depending on the degree of complementarity, miRNA regulates gene expression through mRNA target cleavage, translational repression, or mRNA degradation.

Figure 2

Schematic representation of key cellular processes regulated by miR-28, including proliferation (increase in cell number through division), migration (directed cell movement), epithelial–mesenchymal transition (EMT: a process in which epithelial cells acquire mesenchymal and migratory properties), invasion (the penetration of surrounding tissues), and apoptosis (programmed cell death essential for tissue homeostasis). These processes are central for determining the fate of cells and are frequently dysregulated in pathological conditions, particularly cancer. This figure highlights the regulatory role of miR-28 and its potential implications in disease progression and targeted therapeutic development.

Figure 3

Overview of human cancer types associated with dysregulation of miR-28. The diagram presents a broad spectrum of malignancies in which the aberrant expression or functional disruption of miR-28 was implicated. These include both solid tumors and hematological malignancies, highlighting the pleiotropic nature of miR-28 across diverse tissue types. miR-28 has been associated with sarcomas such as rhabdomyosarcoma; carcinomas of epithelial origin including breast, colorectal, lung, nasopharyngeal, gastric, pancreatic, prostate, ovarian, bladder, esophageal, cholangiocarcinoma, endometrial, hepatocellular, and papillary thyroid cancers; and gliomas representing tumors of glial cell origin and melanomas derived from melanocytes. Additionally, miR-28 is implicated in hematological malignancies such as non-Hodgkin lymphoma, indicating its relevance beyond solid tumors. Dysregulation of miR-28 in these cancers involves diverse mechanisms, including altered expression levels, loss of tumor-suppressive functions, or gain of oncogenic activity, depending on the tumor context. This figure underscores the widespread involvement of miR-28 in tumor biology and supports its relevance as a potential biomarker or therapeutic target across multiple cancer types. Full references and mechanistic details are provided in the main text.