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Updated: May 14, 2026

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Published on: August 23, 2019
RTN4IP1 is down-regulated in thyroid cancer and has tumor-suppressive function
Reza Rahbari1, Mio Kitano, Lisa Zhang
1Endocrine Oncology Branch, Clinical Research Center, 10 Center Drive, MSC 1201, National Cancer Institute, Bethesda, Maryland 20892, USA.
Context:
Previously we identified RTN4IP1 to be differentially expressed in thyroid cancer by sex and the gene is located on chromosome 6q21, a chromosomal region frequently deleted or with loss of heterozygosity in a variety of human malignancies including thyroid cancer.
Objective:
Because the expression and function of this gene is unknown, we sought to characterize its expression in normal, hyperplastic, and benign and malignant thyroid tissue samples and to evaluate its function in cancer cells.
Design:
RTN4IP1 expression was analyzed in normal and hyperplastic thyroid tissue and benign and malignant thyroid tissue samples. In 3 thyroid cancer cell lines (TPC1 from a papillary thyroid cancer, FTC133 from a follicular thyroid cancer, XTC1 from a Hürthle cell carcinoma), small interfering RNA knockdown of RTN4IP1 was used to determine its role in regulating the hallmarks of malignant cell phenotype (cellular proliferation, migration, apoptosis, invasion, tumor spheroid formation, anchorage independent growth).
Results:
We found RTN4IP1 mRNA expression was significantly down-regulated in follicular and papillary thyroid cancer as compared with normal, hyperplastic, and benign thyroid neoplasms (P < .05). Moreover, RTN4IP1 mRNA expression was significantly lower in larger papillary thyroid cancers (P < .05). Small interfering RNA knockdown of RTN4IP1 expression increased cellular proliferation (2- to 4-fold) in all 3 of the cell lines tested and increased cellular invasion (1.5- to 3-fold) and migration (2- to 7.5-fold), colony formation (3- to 6-fold), and tumor spheroid formation (P < .05) in 2 of the 3 cell lines tested (FTC-133 and XTC1).
Conclusions:
This is the first study to characterize the expression and function of RTN4IP1 in cancer. Our results demonstrate RTN4IP1 is down-regulated in thyroid cancer and is associated with larger papillary thyroid cancer and that it regulates malignant cell phenotype. These findings, taken together, suggest that RTN4IP1 has a tumor-suppressive function and may regulate thyroid cancer progression.
Insights
Reticulon 4 interacting protein 1 (RTN4IP1) is down-regulated in thyroid cancer, suggesting a tumor-suppressive role. Its reduced expression correlates with larger tumors and increased cancer cell proliferation and invasion.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Reticulon 4 interacting protein 1 (RTN4IP1) is differentially expressed in thyroid cancer.
- The RTN4IP1 gene is located on chromosome 6q21, a region often altered in malignancies.
Purpose of the Study:
- To characterize RTN4IP1 expression in normal, hyperplastic, and cancerous thyroid tissues.
- To evaluate the functional role of RTN4IP1 in thyroid cancer cell phenotypes.
Main Methods:
- RTN4IP1 mRNA expression analysis in various thyroid tissue types.
- Small interfering RNA (siRNA) knockdown of RTN4IP1 in three thyroid cancer cell lines (papillary, follicular, Hürthle cell).
- Assessment of malignant cell phenotypes: proliferation, migration, invasion, apoptosis, spheroid formation, and anchorage-independent growth.
Main Results:
- RTN4IP1 mRNA expression was significantly lower in follicular and papillary thyroid cancers compared to normal, hyperplastic, and benign tissues.
- Lower RTN4IP1 expression correlated with larger papillary thyroid cancers.
- RTN4IP1 knockdown increased proliferation, invasion, migration, colony formation, and tumor spheroid formation in cancer cell lines.
Conclusions:
- RTN4IP1 is down-regulated in thyroid cancer and linked to larger tumor size.
- RTN4IP1 plays a role in regulating malignant cell phenotypes.
- RTN4IP1 exhibits tumor-suppressive functions and may influence thyroid cancer progression.
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