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Published on: August 23, 2019
Nodal metastasis microRNA expression correlates with the primary tumour in MTC
Justin S Gundara1, Jing Ting Zhao, Anthony J Gill
1Cancer Genetics Laboratory, Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, Sydney, New South Wales, Australia; Endocrine Surgical Unit, Royal North Shore Hospital, St. Leonards, Sydney, New South Wales, Australia; University of Sydney, Sydney, New South Wales, Australia; Northern Translational Cancer Research Unit, Kolling Institute of Medical Research, Royal North Shore Hospital, St. Leonards, Sydney, New South Wales, Australia.
Introduction:
Lymph node metastases represent a diagnostic and management challenge in patients with disseminated medullary thyroid carcinoma (MTC). Our understanding of microRNA (miRNA) profiles of metastatic disease also remains limited and may unveil novel therapeutic strategies for these patients.
Methods:
MTC patients with a history of total thyroidectomy and lymph node dissection were identified from within the prospective Sydney University Endocrine Surgical Unit database. Patients with available formalin-fixed paraffin-embedded tumour tissue were included and clinicopathological data were collated. Total RNA was extracted and quantitave polymerase chain reaction (qPCR) analysis performed on the primary tumour and a corresponding lymph node metastasis for expression of miRNAs of proven significance in MTC (miR-9*, miR-183 and miR-375).
Results:
Tissue was available for analysis in seven patients. The median age at diagnosis was 55 years (range: 22-67). Median tumour size was 18 mm (range: 6-55) and over a median follow-up period of 34 months (range: 1-210), five further operations were undertaken for residual disease. One patient died of metastatic disease. Pairwise correlations of qPCR expression levels between primary tumours and corresponding lymph node metastases revealed significant correlations for miR-9* (P < 0.001), miR-183 (P = 0.001) and miR-375 (P = 0.004).
Conclusion:
miRNA expression patterns in nodal metastases significantly reflect those of the primary tumour in MTC. This further validates previously reported miRNA profile analyses and reiterates the potential significance of miR-9*, -183 and -375 in the pathophysiology of MTC. The possibility of lymph node biopsy miRNA analysis driven clinical decision making may now also be a possibility where conventional techniques are unhelpful.
Insights
MicroRNA (miRNA) expression in medullary thyroid carcinoma (MTC) lymph node metastases mirrors primary tumors. This finding supports using miRNA analysis from lymph node biopsies for MTC diagnosis and treatment decisions.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Lymph node metastases in medullary thyroid carcinoma (MTC) present diagnostic and management challenges.
- Understanding microRNA (miRNA) profiles in metastatic MTC is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate and compare miRNA expression patterns between primary MTC tumors and their corresponding lymph node metastases.
- To assess the potential of specific miRNAs (miR-9*, miR-183, miR-375) in MTC pathophysiology and clinical decision-making.
Main Methods:
- Analysis of formalin-fixed paraffin-embedded tumor tissue from seven MTC patients.
- Quantitative polymerase chain reaction (qPCR) to measure expression levels of miR-9*, miR-183, and miR-375 in primary tumors and lymph node metastases.
Main Results:
- Significant correlations were observed between primary tumors and lymph node metastases for miR-9* (P < 0.001), miR-183 (P = 0.001), and miR-375 (P = 0.004).
- Clinicopathological data including age, tumor size, and follow-up revealed disease progression in some patients.
Conclusions:
- miRNA expression profiles in MTC lymph node metastases are highly reflective of the primary tumor.
- The study validates the significance of miR-9*, miR-183, and miR-375 in MTC.
- Lymph node biopsy miRNA analysis may offer a new avenue for clinical decision-making in MTC management.
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