Ferroptosis and non-coding RNAs in lung cancer: exploring molecular mechanisms and diagnostic/therapeutic implications
Xue et al. Cancer Cell International
(2025) 25:364
https://doi.org/10.1186/s12935-025-03949-x
Cancer Cell International
Open Access
REVIEW
Ferroptosis and non-coding RNAs in lung
cancer: exploring molecular mechanisms
and diagnostic/therapeutic implications
Hedong Xue1, Melika Malek2* and Liangyu Li3,4*
Abstract
Lung cancer is the second most prevalent type of cancer on a global scale, and is widely known for being the
deadliest. Revealing the fundamental molecular mechanisms of this condition has the potential to unlock fresh
possibilities and avenues for managing it. Ferroptosis is a newly discovered type of controlled cell death that
distinguishes itself from traditional forms of programmed cell death, specifically apoptosis and necrosis, through its
distinct biochemical and structural characteristics. Changes made to the mechanism that regulates ferroptosis can
have a significant influence on the development of various illnesses, such as, though not limited to, lung cancer.
Based on scientific studies, it has been proven that cancer cells possess a significant capability to inhibit ferroptosis,
leading to their continuous growth and survival. The presence of non-coding RNAs has a profound influence on
controlling a wide range of cellular functions, with a particular focus on cancer. They have been closely associated
with all key features of lung cancer. Fresh findings have indicated that these particles also have the task of
controlling ferroptosis. Thus, the use of non-coding RNA as a therapeutic strategy offers a potentially effective
option for regulating ferroptosis in the management of cancer. The main focus of this overview is on ncRNAs and
their function in controlling ferroptosis, specifically within the context of lung cancer.
Keywords Ferroptosis, Non-coding RNAs, Lung cancer, Cell death, Molecular mechanisms
*Correspondence:
Melika Malek
Liangyu Li
1
Department of Urology, The First People’s Hospital of Pinghu,
Pinghu 314200, Zhejiang, China
2
Shahid Beheshti University of Medical Sciences, Tehran, Iran
3
Cancer Center, Department of Pulmonary and Critical Care Medicine,
Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital),
Hangzhou Medical College, Hangzhou 310005, Zhejiang, China
4
Department of Nursing, Zhejiang Provincial People’s Hospital, Affiliated
People’s Hospital, Hangzhou Medical College, Hangzhou 310005,
Zhejiang, China
Introduction
Cancer is a disease where cells grow and spread uncontrollably, often resulting in its spread to other areas of
the body. It typically has a hidden onset and a prolonged
course of treatment [1, 2]. Based on the latest figures from
the American Cancer Society as of 2020, lung cancer
remains a prevalent type of cancer and remains the leading cause of cancer-related fatalities globally [3, 4]. There
are two main types of lung cancer: non-small cell lung
cancer (NSCLC) and small cell lung cancer (SCLC). Nonsmall cell lung cancer, also known as NSCLC, is the most
common type of lung cancer, accounting for approximately 85–90% of all diagnosed cases. When looking at
SCLC and NSCLC, NSCLC tends to develop at a slower
rate and have a more optimistic forecast [5]. A novel
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Xue et al. Cancer Cell International
(2025) 25:364
form of cellular death has been revealed, regulated by
the existence of iron and the consequent oxidation of lipids [6]. Understanding the procedures and mechanisms
of cellular demise is crucial in the effort to prevent and
treat cancer. Additional forms of cellular demise mechanisms consist of necrosis, apoptosis, and pyroptosis. The
advance of lung cancer heavily relies on the evolution of
ferroptosis, similar to numerous other forms of cancer.
The development of lung cancer is greatly impacted by
the interconnected interactions of vital signaling molecules, including epidermal growth factor receptors,
mitogen-activated protein kinase, hypoxia-inducible
factor, tumor suppressor P53, and mammalian target of
rapamycin. The presence of these compounds is crucial
for the rise in cases of lung cancer. However, the control
of ferroptosis encompasses a diverse range of non-coding
RNA molecules such as microRNA, long non-coding
RNA, and circular RNA [7]. Ferroptosis refers to the
physiological process in which cells are destroyed due to
an overwhelming level of oxidative stress. This method of
cell demise stands out from others like necrosis, autophagy, and apoptosis in terms of its distinctiveness. The reason for this phenomenon is the inhibition of the body’s
natural defense system against damaging oxidants, which
occurs when the level of reduced glutathione (GSH) in
cells decreases. Hence, the formation of harmful reactive
oxygen species (ROS) is greatly influenced by lipids [8].
The p53 protein plays a key role in the effectiveness of
ferroptosis, which plays a crucial role in hindering tumor
growth in this specific situation [9]. In addition, a multitude of research has indicated a link between the mechanism of lipid peroxidation, build-up of iron, and the onset
of ferroptosis [10, 11].
NcRNAs, otherwise known as non-coding RNAs,
encompass a wide range of transcripts that do not possess the capability to generate proteins. Despite the fact
that they have limitations, they are essential for many cellular functions because of their unique molecular mechanisms [6]. Initially, it was thought that their purpose
held little significance. The idea that proteins are the sole
functional outcome of gene expression has significantly
shifted with the discovery and analysis of numerous functional ncRNAs [7]. In broad terms, these particles can be
categorized into two primary categories: short or long
non-coding RNAs, depending on their specific lengths
(typically no more than 200 nucleotides), or organized
according to their diverse functions and objectives [8].
Functional non-coding RNAs come in three main types –
microRNAs (short), long non-coding RNAs, and circ (...truncated)
