**6. Anaplastic thyroid cancer and liquid biopsy**

Anaplastic thyroid carcinoma (ATC) is aggressive thyroid tumor which consists of undifferentiated follicular thyroid cells [14].

Many miRNAs have been found to be dysregulated in thyroid cancer, but only a few miRNAs are exclusively dysregulated in anaplastic thyroid cancer (ATC) [28]. Loss of miR-200 expression in ATC results in epithelial-mesenchymal transition (EMT) that represses the epithelial features of cancer cells and disrupts the cell-cell adhesion mediated by the loss of E-cadherin. This process enables cells to migrate and invade [26–28].

Overexpression of the miR-17-92 cluster results in downregulation of tumor suppressor PTEN. This process potentiates the activation of AKT/mTOR growth and survival signaling. Another important tumor-suppressive pathway targeted by miR-17-92 is the TGFβ signaling pathway [28]. Increase of miR-17-92 leads to a loss of the tumor inhibitory effect of TGFβ in thyroid cancer cells, which enhances cell proliferation [26–28].


**Table 4.** Expression of microRNA in ATC.

in follicular thyroid cancers (FTC) are also frequently present in other subtypes of thyroid cancer [27]. miR-199a-5p is downregulated, but miR-197 and miR-346 are upregulated in FTC

**Type of regulation Outcome References**

proliferation

proliferation

proliferation

Medullary thyroid cancer (MTC) accounts for only 5% of thyroid cancers; it is responsible for approximately 13% of all thyroid cancer-related deaths [4]. MTC is a malignant thyroid tumor showing evidence of C-cell differentiation [14]. One of the recently studied miRNAs in medullary thyroid cancer is miR-21, which is downregulated especially in the aggressive forms [27]. miR-129-5p also is significantly downregulated in MTC compared to normal tis-

**Type of regulation Outcome References**

metastatic disease

metastatic disease

Aggressive behavior and metastatic disease

Decreased cellular apoptosis and increased cell migration

Rodriguez-Rodero et al. [27]

Rodriguez-Rodero et al. [27] Boufraqech et al. [28]

Rossi et al. [21] Boufraqech et al. [28]

Rossi et al. [21] Boufraqech et al. [28]

Rodriguez-Rodero et al. [27]

Rodriguez-Rodero et al. [27]

Rodriguez-Rodero et al. [27] Boufraqech et al. [28]

Accardo et al. [35]

Accardo et al. [35] Boufraqech et al. [28]

Accardo et al. [35] Boufraqech et al. [28] Pennelli et al. [36]

leading to increased cancer cell proliferation [28] (**Table 2**).

Follicular cancer miR-199a-5p Downregulated in cells Increased cellular

miR-197 Upregulated in cells Increased cellular

miR-346 Upregulated in cells Increased cellular

**5. Medullary thyroid cancer and liquid biopsy**

miR-21 Downregulated in tissue

miR-129-5p Downregulated in tissue

**Diagnosis Type of** 

**Diagnosis Type of** 

92 Liquid Biopsy

**miRNA**

**Table 2.** Expression of microRNA in FTC.

Medullary thyroid

cancer

**miRNA**

**Table 3.** Expression of microRNA in MTC.

sue leading to increased cellular invasion and migration [28] (**Table 3**).

miR-183 Upregulated in tissue Aggressive behavior and

miR-375 Upregulated in tissue Aggressive behavior and

miR-30 plays a role in thyroid cancer differentiation and progression. Overexpression of miR-30 family members leads to a change in cell morphology and decreased vimentin expression in cancer cells [28]. This is suggesting that miR-30 family members are involved in cancer progression by regulating the EMT process [26–28] (**Table 4**).

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