Effects of let-7 microRNA on cell growth and differentiation of papillary thyroid cancer

Júlio Cezar Marques Ricarte-Filho, Cesar Seigi Fuziwara, Alex Shimura Yamashita, Eloiza Rezende, Marley Januário Da-Silva, Edna Teruko Kimura

Research output: Contribution to journalArticlepeer-review

Abstract

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy and RET/PTC rearrangements represent key genetic events frequently associated to this cancer, enhancing proliferation and dedifferentiation by activation of the RET/PTC-RAS-BRAF-mitogen-activated protein kinase (MAPK) pathway. Recently, let-7 microRNA was found to reduce RAS levels in lung cancer, acting as a tumor suppressor gene. Here, we report that RET/PTC3 oncogenic activation in PCCL3 rat thyroid cells markedly reduces let-7f expression. Moreover, stable transfection of let-7 microRNA in TPC-1 cells, which harbor RET/PTC1 rearrangement, inhibits MAPK activation. As a result, let-7f was capable of reducing TPC-1 cell growth, and this might be explained, at least in part, by decreased messenger RNA (mRNA) expression of cell cycle stimulators such as MYC and CCND1 (cyclin D1) and increased P21 cell cycle inhibitor mRNA. In addition, let-7 enhanced transcriptional expression ofmolecular markers of thyroid differentiation such as TITF1 and TG. Thus, reduced expression of let-7f might be an essential molecular event in RET/PTC malignant transformation. Moreover, let-7f effects on thyroid growth and differentiation might attenuate neoplastic process of RET/PTC papillary thyroid oncogenesis through impairment of MAPK signaling pathway activation. This is the first functional demonstration of an association of let-7 with thyroid cancer cell growth and differentiation.

Original languageEnglish (US)
Pages (from-to)236-241
Number of pages6
JournalTranslational Oncology
Volume2
Issue number4
DOIs
StatePublished - 2009
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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