miRNA Expression in a Human Papillary Thyroid Carcinoma Cell Line Varies with Invasiveness

Abstract

Abstract. The purpose of these studies was to explore the expression pattern of miRnAs associated with invasion and metastasis of human papillary thyroid carcinoma (pTC). A transwell invasion chamber was used to select progressively more invasive cancer cell populations from a clonal cell line of human pTC with cervical lymph node metastasis, ihh-4. Three sublines with progressive invasiveness, designated ihh-4M-1, ihh-4M-2 and ihh-4M-3, were obtained through this in vitro selection process. The sublines manifested an increase in colony-forming ability on soft agar and metastatic potency in nude mice. Then metastasis-related miRnAs differentially expressed between them were analyzed utilizing the miRnA microarray technique. We found that 11 metastasis-related miRnAs were differentially expressed between the invasive subpopulations and their control subpopulations; these miRNAs may account for their significant difference in the invasion capabilities and favor lymphatic metastasis of pTC.Key words: miRnA, papillary thyroid carcinoma, invasiveness PTC is the most common type of thyroid malignancy; it accounts for approximately 80% of all thyroid cancers. Micro-RnAs (miRnAs) are small, noncoding RnAs that regulate gene expression by reducing the stability of conventional mRnAs and/or inhibiting their translation into proteins [1]. Over the past few years, characteristic miRNA expression profiles have been identified that enable tumor classification and prognostication and various individual miRnAs have been described as oncogenes or tumor suppressors [2][3][4]. Several recent studies have identified specific miRnAs that are central to metastatic progression. however, little is known about the expression of miRnAs in pTC, or about their utility as biomarkers for predicting metastatic behavior and clinical outcome.invasion and metastasis are closely correlated during the development and progression of tumors. The migration and metastasis of cancer cells takes place in three steps: adherence, degradation, and movement. Tumor cells must initiate and successfully complete all of these steps in order to enter the circulatory and lymphatic systems to form distant metastases [5,6]. in order to study mechanisms accompanying each invasive step, several in vitro invasion models have been developed and can be used to assess the invasive activity of various tumor cells [7,8]. To gain insight into alterations in metastasis related miRnA expression that might govern lymphatic metastasis of pTC, we previously established highly metastatic pTC cell lines (designated ihh-4M-1, ihh-4M-2 and ihh-4M-3) from a clonal cell line of human pTC (ihh-4) through in vitro selection using a transwell invasion chamber. We compared the in vitro tumorigenicity and in vivo metastatic capabilities of these sublines by colony-formation assay and xenograft nude mouse model and found that metastatic tumor cells showed signifi-

MicroRNA Expression Profiles in the Management of Papillary Thyroid Cancer

“…In one of the earliest studies on this subject, Gao et al demonstrated miRNA differential expression in three subpopulations of a PTC cell line (IHH-4) with increased lymph node metastatic potency compared with the control subpopulations [41]. They found that 11 miRNAs from the array of 509 miRNAs were significantly differentially expressed among 3 pairs of subpopulations with high and low metastatic potential.…”

Deregulation of microRNA expression in thyroid tumors

“…The migration and metastasis of cancer cells take place in three steps: adherence, degradation, and movement (Gao et al, 2010). In order to invade the circulatory and lymphatic systems to get metastasis, the tumor cells must initiate and completely come through all of these steps (Ponta et al, 2001).…”

“…In order to invade the circulatory and lymphatic systems to get metastasis, the tumor cells must initiate and completely come through all of these steps (Ponta et al, 2001). Gao et al (2010) have done experiments between highly metastatic PTC cell lines and common human PTC cell lines to illustrate the relationship between deregulated miRNAs and metastasis of PTCs. The results showed that 11 miRNAs were differentially expressed in the metastatic and control cell lines.…”

A Panel of Four miRNAs Accurately Differentiates Malignant from Benign Indeterminate Thyroid Lesions on Fine Needle Aspiration

“…In cancer, miRNAs have been shown to function as both tumor suppressors or oncogenes and have been useful for cancer classification and prognostication (8). miRNAs have been reported to be dysregulated in virtually all human cancer types, including all variants of thyroid cancer (9)(10)(11). miR-222, miR-181a, and miR-146b have been shown to be upregulated at least 10-fold in several studies when comparing classic variants of papillary thyroid carcinoma (CPTC) to normal thyroid tissue (12,13).…”