Surreal illustration of a thyroid gland with RNA strands.

Decoding Thyroid Cancer: How a Tiny RNA Could Change Everything

Beau Callahan in Health & Wellness December 2025 • 4 min read.

"New research unveils the role of CCAL in papillary thyroid cancer, paving the way for targeted therapies and improved patient outcomes."

Thyroid cancer, a prevalent endocrine malignancy, has been on the rise in recent years. Papillary thyroid carcinoma (PTC) accounts for approximately 80% of all thyroid tumors, making it essential to understand its underlying mechanisms. While surgery combined with radioiodine and levothyroxine treatment is the primary approach, many PTC-related deaths occur annually, highlighting the need for effective diagnostic biomarkers and therapeutic targets.

Long noncoding RNAs (lncRNAs) have emerged as key players in various biological processes, including cell development, immune regulation, and tumorigenesis. These transcripts, longer than 200 nucleotides, lack protein-coding potential but exert crucial functions in cancer development and progression. Research suggests that dysregulation of lncRNAs is closely linked to tumor development, influencing cellular proliferation, apoptosis, migration, and invasion.

A particular lncRNA, colorectal cancer-associated lncRNA (CCAL), has been identified as an oncogene in various cancers, including hepatocellular carcinoma, osteosarcoma, and colorectal cancer. However, its role in PTC has remained largely unexplored. A groundbreaking study has now uncovered the significance of CCAL in promoting papillary thyroid cancer progression through the activation of the NOTCH1 pathway.

How Does CCAL Influence Thyroid Cancer?

Surreal illustration of a thyroid gland with RNA strands.

A recent study investigated the expression of CCAL in PTC tissues and adjacent normal tissues. Results indicated that CCAL was significantly upregulated in PTC tissues compared to normal tissues. The study further revealed a positive correlation between CCAL expression and PTC severity and TNM stage, suggesting that higher CCAL levels are associated with more advanced disease stages. Survival analysis demonstrated that patients with higher CCAL expression had worse overall survival rates.

To explore the functional role of CCAL in PTC, researchers conducted in vitro experiments using PTC cell lines. Knockdown of CCAL significantly inhibited cell proliferation, migration, and invasion. Conversely, overexpression of CCAL promoted these processes. These findings suggest that CCAL plays a crucial role in driving PTC cell growth and metastasis.

CCAL promotes cancer cell growth.
CCAL is linked to later stage cancer.
CCAL promotes the migration of cancer cells.

To uncover the underlying mechanisms, the study focused on the NOTCH1 signaling pathway, known for its involvement in tumor growth and metastasis. Knockdown of CCAL dramatically decreased the expression of NOTCH1 and suppressed its activation. Overexpression of NOTCH1 rescued the proliferation, migration, and invasion in PTC cells. These results suggest that CCAL promotes PTC development and progression by activating the NOTCH1 pathway.

What's Next in Thyroid Cancer Research?

This study sheds light on the critical role of CCAL in promoting papillary thyroid cancer progression through activation of the NOTCH1 pathway. These findings offer new insights into the molecular mechanisms driving PTC development and provide a potential target for therapeutic interventions. Further research is warranted to explore the clinical implications of these findings and to develop novel strategies targeting the CCAL/NOTCH1 axis for the treatment of papillary thyroid cancer.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.3727/096504018x15188340975709, Alternate LINK

Title: Long Noncoding Rna Ccal Promotes Papillary Thyroid Cancer Progression By Activation Of Notch1 Pathway

Subject: Cancer Research

Journal: Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics

Publisher: Cognizant, LLC

Authors: Ying Ye, Yanan Song, Juhua Zhuang, Saifei He, Jing Ni, Wei Xia

Published: 2018-10-17

Everything You Need To Know

What is papillary thyroid cancer, and why is it important to study?

Papillary thyroid carcinoma (PTC) is a prevalent form of thyroid cancer, accounting for approximately 80% of thyroid tumors. It is a significant area of research because despite existing treatments like surgery, radioiodine, and levothyroxine, a considerable number of deaths occur annually. This highlights the need for more effective diagnostic tools and therapies, making understanding PTC's underlying mechanisms crucial for improving patient outcomes.

What is CCAL, and what role does it play in cancer?

CCAL, or colorectal cancer-associated long noncoding RNA, is a specific type of lncRNA. These are long noncoding RNAs longer than 200 nucleotides that do not code for proteins. Research has identified CCAL as an oncogene in various cancers, including hepatocellular carcinoma, osteosarcoma, and colorectal cancer. The significance of CCAL lies in its role in promoting cancer progression. In the context of papillary thyroid cancer, CCAL is upregulated in PTC tissues and is associated with more advanced disease stages and worse survival rates. Its presence and activity are directly linked to the growth, migration, and invasion of cancer cells, making it a key factor in PTC development.

How does CCAL influence the NOTCH1 pathway?

The NOTCH1 pathway is a signaling pathway involved in tumor growth and metastasis. The study reveals that CCAL promotes papillary thyroid cancer progression by activating the NOTCH1 pathway. When CCAL is present, it increases the activity of NOTCH1, which in turn drives the growth and spread of PTC cells. The study demonstrates that suppressing CCAL decreases NOTCH1 expression and activity, hindering cancer cell proliferation, migration, and invasion. Understanding the relationship between CCAL and the NOTCH1 pathway offers a potential target for therapeutic interventions.

What is the significance of CCAL levels in papillary thyroid cancer?

In the context of papillary thyroid cancer, higher levels of CCAL expression are associated with more advanced disease stages (TNM stage) and worse overall survival rates. This means that patients with higher levels of CCAL in their tumor tissues tend to have more aggressive cancer and a poorer prognosis. Furthermore, when CCAL is knocked down in cancer cells, their growth, migration, and invasion are inhibited, suggesting that CCAL actively drives the progression of PTC.

What are the potential implications of these findings for treating thyroid cancer?

The research suggests that CCAL could be a valuable target for future therapies. By targeting the CCAL/NOTCH1 axis, researchers aim to develop new strategies to treat papillary thyroid cancer. This might involve drugs or other interventions designed to block CCAL's function, thereby inhibiting the activation of the NOTCH1 pathway and slowing down cancer progression. This approach could lead to more effective treatments and improved outcomes for patients diagnosed with papillary thyroid cancer.