# The Interplay Between lncRNAs–microRNAs Network Dysregulation and Cellular Hallmarks of Thyroid Cancer

## TL;DR

This review explores how lncRNAs and microRNAs contribute to thyroid cancer development and progression, offering potential for new diagnostics and treatments.

## Contribution

The paper systematically reviews the dysregulation of lncRNA–microRNA networks in thyroid cancer and their links to cancer hallmarks.

## Key findings

- Dysregulated lncRNAs contribute to multiple cancer hallmarks, including immune evasion and metabolic reprogramming.
- Notable lncRNAs like H19, MALAT1, and DOCK9-AS2 are linked to aggressive thyroid cancer and could serve as biomarkers.
- New technologies like single-cell RNA sequencing may improve understanding of lncRNA–microRNA networks in thyroid cancer.

## Abstract

Thyroid cancer is the most common type of endocrine tumor, and its aggressive forms remain difficult to treat. In recent years, researchers have discovered that two types of non-coding RNAs, called long non-coding RNAs (lncRNAs) and microRNAs, play an important role in the behavior of thyroid cancer cells. These molecules do not make proteins but instead regulate how other genes are switched on or off. When their normal balance is disturbed, they can drive cancer cells to grow faster, spread to other tissues, or escape the body’s immune defenses. This review explains how changes in lncRNA–microRNA networks are connected to the main features of thyroid cancer, such as uncontrolled growth, resistance to cell death, and altered metabolism. Understanding these networks may open the way to new diagnostic tools and personalized treatments that target RNA molecules, improving outcomes for patients with thyroid cancer.

Background/Objectives: Thyroid cancer (TC) is the most common type of endocrine neoplasm and is increasing in incidence, particularly papillary thyroid carcinoma (PTC). Early-stage disease has a favorable prognosis; however, advanced forms, such as anaplastic thyroid carcinoma, complicate treatment. Long non-coding RNAs (lncRNAs), longer than 200 nucleotides and non-coding, together with microRNAs, have emerged as major regulators of TC pathogenesis. This review summarizes data on how dysregulated lncRNAs influence the hallmarks of cancer in thyroid malignancies. Methods: We reviewed the literature on the role of lncRNAs and microRNAs in TC, focusing on their functions as competing endogenous RNAs (ceRNAs), regulators of PI3K/AKT and Wnt/β-catenin pathways, and controllers of epigenetic alterations. Results: Dysregulated lncRNAs contribute to hallmarks including sustained growth, evading suppressors, resisting death, replicative immortality, angiogenesis, invasion, metabolic reprogramming, immune evasion, genomic instability, and tumor-promoting inflammation. ceRNA mechanisms amplify immune evasion by regulating checkpoint proteins and cytokines, altering immune cell activity. Altered lncRNA profiles correlate with aggressiveness, metastasis, and prognosis. Notable lncRNAs, such as H19, MALAT1, and DOCK9-AS2, dysregulate oncogenic pathways and represent potential biomarkers. Conclusions: Advances in therapeutics suggest inhibiting oncogenic lncRNAs or restoring tumor-suppressive lncRNAs via RNA interference, antisense oligonucleotides, or CRISPR/Cas9 editing. New technologies, including single-cell RNA sequencing and spatial transcriptomics, will improve understanding of heterogeneous lncRNA–microRNA networks in TC and support precision medicine. LncRNAs signify both molecular drivers and clinical targets for thyroid cancer.