Surreal illustration of a thyroid gland with RNA strands.

Decoding Thyroid Cancer: How a Tiny RNA Could Change Everything

Beau Callahan in Health & Wellness October 2026 • 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.

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Stats & Impact

Thyroid Function and Disease

The thyroid is an endocrine gland that makes and releases hormones, with its main job being to control metabolism and how the body uses energy. Thyroid disease is a general term for conditions in which the gland does not make the right amount of hormones, and hypothyroidism is identified as the most common type. Research on papillary thyroid cancer also examines colorectal cancer-associated lncRNA (CCAL), proliferation, migration, and NOTCH1.

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.

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Latest Research

RNA Pathways Under Study

Research on papillary thyroid carcinoma reports that miR-26a-5p may be a potentially effective target gene, with links to Wnt5a, invasion, and metastasis. Another source reports that CCAL promotes papillary thyroid cancer progression by activating the NOTCH1 pathway. Findings on Notch 1 signaling indicate that its activation can increase papillary thyroid carcinoma cell proliferation, migration, and invasion in vitro while preventing tumor growth and metastasis in vivo.

Counterpoints

Evidence Still Developing

One study reports that knocking down CCAL significantly inhibited papillary thyroid cancer cell proliferation, migration, and invasion in vitro and reduced tumor growth and metastasis in vivo. However, another source states that whether CCAL plays a role in papillary thyroid carcinoma remained to be explored. Together, these sources show that experimental findings support a possible role for CCAL, while its relevance to PTC was not presented as fully established.

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.

What the CCAL experiments add to the picture

In cell experiments, reducing CCAL altered several NOTCH1 pathway markers, and restoring NOTCH1 activity in CCAL-silenced cells tested whether the pathway could account for the cellular effects. The experiments support a pathway link in these models, not proof of a clinical effect in patients.^[1]

What limits the CCAL-NOTCH1 interpretation

The authors also said CCAL’s role in PTC remained to be explored, underscoring that their results did not resolve the question fully.^[1]
The reported functional evidence includes cell assays; those results do not by themselves establish how the pathway behaves across patients or clinical care.^[1]

The PTC tissue cohort and mouse observation period

Sample size	52 PTC tissues and 52 normal tissues^[2]
Duration	7 weeks^[2]
Funding	Natural Science Foundation of China (No. 81571718); Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai (PWZxk2017-06); Science and Technology Development Fund (14DZ1940605); Science and Technology Development Fund of Shanghai Pudong New Area (PKJ2017-Y14); Talents Training Program of the Seventh People’s Hospital of Shanghai University of TCM (Grant No. XX2017-04)^[2]
Times cited	12^[2]

How the CCAL study fits alongside related findings

Other thyroid-cancer lncRNAs, including MALAT1, HIT000218960, and HOTAIR, have also been reported in relation to progression; CCAL is part of a broader research area rather than the only RNA under study.^[1]

Questions the CCAL results leave open

Would the expression pattern and survival association hold in a larger or independent patient group?^{[1] [2]}
How closely do the experimental findings in cells and mice reflect tumor behavior in patients?^[2]

Terms used in the CCAL study

H3K4me3: An active histone modification.^[1]

Sources

Long Noncoding RNA CCAL Promotes Papillary Thyroid Cancer Progression by Activation of NOTCH1 Pathway (Europe PMC, 2018)
Long Noncoding RNA CCAL Promotes Papillary Thyroid Cancer Progression by Activation of NOTCH1 Pathway (Tech Science Press, 2018)

About this Article -

Written with AI assistance from published research, and reviewed by the Mystum team. 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.