MicroRNA-146b: A Novel Biomarker and Therapeutic Target for Human Papillary Thyroid Cancer

Abstract

Papillary thyroid cancer (PTC) is the most common tumor subtype of thyroid cancer. However, not all PTCs are responsive to current surgical and radioiodine treatment. The well-established clinical prognostic factors include tumor size, lymph node/distal metastasis, and extrathyroidal invasion. The RET/PTC-RAS-BRAF linear molecular signaling cascade is known to mediate PTC pathogenesis. However, whether presence of BRAF mutation, the most common genetic alteration in PTC, can affect PTC behavior and prognosis is controversial. MicroRNAs (miRNAs) have been labeled as promising molecular prognostic markers in several tumor types. Our recent studies demonstrated that microRNA-146b (miR-146b) deregulation is associated with PTC aggressiveness and prognosis. Here we summarize the current knowledge related to the functional roles, regulated target genes, and clinical applications of miR-146b in PTC and discuss how these studies provide insights into the key role of miR-146b as an oncogenic regulator promoting cellular transformation as well as a prognosis marker for tumor recurrence in PTC. In conjunction with the current perspectives on miRNAs in a wide variety of human cancers, this review will hopefully translate these updated findings on miR-146b into more comprehensive diagnostic or prognostic information regarding treatment in PTC patients before surgical intervention and follow up strategies.

Peer Review #2 of "Bioinformatic analysis and identification of potential prognostic microRNAs and mRNAs in thyroid cancer (v0.2)"

“…Geraldo et al stated that miR-146b-5p was highly expressed in papillary thyroid cancer and considered as a relevant diagnostic marker for this type of thyroid cancer. MiR-146b-5p was reported to promote the migration and invasion of papillary thyroid cancer cells via downregulating ZNRF3 and upregulating Wnt/catenin signaling pathway, and to promote thyroid follicular cell growth via downregulating TGF-β pathway by binding to the 3'-untranslated region of SMAD4 (Chou et al 2017;Deng et al 2015;Geraldo et al 2012). Inversely, the expression levels of miR-146b was positively related to the overall survival of patients with thyroid cancer.…”

MicroRNA‐146b overexpression associates with deteriorated clinical characteristics, increased International Staging System stage, cacoethic chromosome abnormality, and unfavorable prognosis in multiple myeloma patients

“…MiR‐146b is one of the negative regulators of nuclear factor‐kappa B (NF‐κB) pathway, whose dysregulation has been found in several hematologic malignancies . It is reported that the overexpression of miR‐146b in microvesicles promotes the transformation of hematopoietic cells to a leukemic state by repressing tumor suppressor gene NUMB .…”

Current Advances in Thyroid Cancer Management. Are We Ready for the Epidemic Rise of Diagnoses?

“…Recently, miRNAs have demonstrated their role in TC progression and as potential markers of malignant thyroid tumors. An increased aberrant expression of some miRNA, mainly miR-222, miR-221, and miR-146b in PTCs, comparing to normal thyroids was reported, with the last one significantly associated with aggressive form of BRAF-positive PTCs [ 110 ]. Moreover, up-regulated expression of miR-146b was present mainly in PTCs (89%) and FVPTCs (41%), but not in FTCs, ATCs, PDTCs, or FAs (7%, 8%, 0% and 0%, respectively) [ 111 ].…”