Circular RNAs in EMT-driven metastasis regulation - modulation of cancer cell plasticity, tumorigenesis and therapy resistance

Sep 21, 2026

Uploaded by Eliana

Non-coding RNAs shape cancer biology, with circular RNAs (circRNAs) standing out for their closed-loop structure and stability. CircRNAs support cancer diagnosis and prognosis and regulate proliferation and metastasis, which drive most cancer deaths. During EMT, epithelial-to-mesenchymal reprogramming elevates N-cadherin and vimentin, alters polarity, and contributes to therapy resistance. This review explains how circRNAs coordinate EMT and influence chemotherapy and radiotherapy responses.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages25

Reading Time1 h 3 min

AccessFree to download

Abstract

Keywords

Introduction

EMT as a hallmark of metastasis

Molecular pathways and regulation of EMT

The function of EMT in tumorigenesis

Cellular and Molecular Life Sciences (2024) 81:214 [https://doi.org/10.1007/s00018-024-05236-w](https://doi.org/10.1007/s00018-024-05236-w) Cellular and Molecular Life Sciences REVIEW Circular RNAs in EMT-driven metastasis regulation: modulation of cancer cell plasticity, tumorigenesis and therapy resistance Milad Ashrafizadeh1,2,3 · Jingyuan Dai4 · Pedram Torabian5,6 · Noushin Nabavi7 · Amir Reza Aref8,9 · Alaa A. A. Aljabali10 · MurtazaTambuwala11,14 · Minglin Zhu12,13 Received: 5 December 2023 / Revised: 5 March 2024 / Accepted: 3 April 2024 © The Author(s) 2024 Abstract The non-coding RNAs comprise a large part of human genome lack of capacity in encoding functional proteins. Among various members of non-coding RNAs, the circular RNAs (circRNAs) have been of importance in the pathogenesis of human diseases, especially cancer. The circRNAs have a unique closed loop structure and due to their stability, they are potential diagnostic and prognostic factors in cancer. The increasing evidences have highlighted the role of circRNAs in the modulation of proliferation and metastasis of cancer cells. On the other hand, metastasis has been responsible for up to 90% of cancer-related deaths in patients, requiring more investigation regarding the underlying mechanisms modulating this mechanism. EMT enhances metastasis and invasion of tumor cells, and can trigger resistance to therapy. The cells demonstrate dynamic changes during EMT including transformation from epithelial phenotype into mesenchymal phenotype and increase in N-cadherin and vimentin levels. The process of EMT is reversible and its reprogramming can disrupt the progression of tumor cells. The aim of current review is to understanding the interaction of circRNAs and EMT in human cancers and such interaction is beyond the regulation of cancer metastasis and can affect the response of tumor cells to chemotherapy and radiotherapy. The onco-suppressor circRNAs inhibit EMT, while the tumor-promoting circRNAs mediate EMT for acceleration of carcinogenesis. Moreover, the EMT-inducing transcription factors can be controlled by circRNAs in different human tumors. Keywords RNA transcripts · circRNAs · cancer malignancy · EMT · cancer cell plasticity · Drug resistance Introduction Since cancer mortality is associated with metastasis, it is essential to emphasize the role of factors that regulate tumor invasion [1] . Therefore, improving treatment and the survival of patients rely on reducing invasion and the malignancy of tumors. Metastasis is one of the hallmarks of tumor and was coined in 1829 by Jean Claude [2] . The word“metastasis” has Greek roots and means “displacement”, with “meta” meaning next and “statis” meaning placement [3] . Metastasis refers to the process in which tumor cells migrate to another part of the body from their primary site to form new cancer cells, leading to death [4] . Cancer metastasis can be modulated via various mechanisms, such as EMT. Increasing evidence reveals that EMT mechanisms have a potential role in tumor invasion and drug insensitivity (Fig. 1) . EMT causes a loss of cell-cell and cell-extracellular matrix adhesion, causing cells with a mesenchymal phenotype to detach from their primary site and separate from surrounding tissues. The process of EMT is not only vital for cancer metastasis but is essential for embryogenesis, tissue fibrosis, and wound healing [6] . Upon EMT induction, the motility of cancer cells increases, and epithelial cells lose their apical-basal polarity in order to transform into mesenchymal cells [7] . The generation of adherens junctions by E-cadherin is vital for cell adhesion and polarity in epithelia and leads to cell-cell attachment and recruitment of signaling complexes [8, 9] . The earliest step in the process of EMT is the loss of E-cadherin levels. EMT-TFs mediate epithelial reorganization via changing and decreasing Extended author information available on the last page of the arti

FAQs

Why are circular RNAs (circRNAs) considered important in cancer?

CircRNAs have a unique closed-loop structure and high stability. Their role in regulating proliferation and metastasis makes them potential diagnostic and prognostic factors in cancer.

How does EMT contribute to metastasis and treatment failure?

EMT enhances invasion and metastasis by switching epithelial cells toward a mesenchymal phenotype and increasing EMT markers. These dynamic changes can also trigger resistance to therapy.

What is the focus of the review regarding circRNAs and EMT?

The review analyzes how circRNAs interact with EMT in human cancers. It highlights that onco-suppressor circRNAs can inhibit EMT, whereas tumor-promoting circRNAs mediate EMT and may affect responses to chemotherapy and radiotherapy.

Sep 21, 2026

Uploaded by Eliana