Novel role of lncRNAs regulatory network in papillary thyroid cancer

Abstract

Papillary thyroid cancer (PTC) is the most common endocrine malignancy. The incidence of PTC has increased annually worldwide. Thus, PTC diagnosis and treatment attract more attention. Noncoding RNAs (lncRNAs) play crucial roles in PTC progression and act as prognostic biomarkers. Moreover, microRNAs (miRNAs) and epithelial-mesenchymal transition (EMT)-associated proteins have potential biomarkers for diagnosing and treating PTC. However, the correlation of lncRNAs with miRNAs and EMT-associated proteins needs further clarification. The present review highlights the recent advances of lncRNAs in PTC. We significantly summarized the two molecular regulatory mechanisms in PTC progress, including lncRNAs-miRNAs-protein signaling axes and lncRNAs-EMT pathways. This review will help our understanding of the association between lncRNAs and PTC and may assist us in evaluating the prognosis for PTC patients. Taken together, targeting the lncRNAs regulatory network has promising applications in diagnosing and treating PTC.

Keywords: Diagnosis; EMT; Papillary thyroid cancer; Prognosis; lncRNAs; miRNAs.

Fig. 1

LncRNAs' correlation with miRNAs and EMT-associated proteins in proliferation and metastasis of papillary thyroid carcinoma (PTC).

Fig. 2

Seven types of lncRNAs-miRNAs-proteins and their effects on PTC. LncRNAs competitively bind miRNAs with mRNA, resulting in the mRNAs of tumor-associated proteins not being degraded, thereby promoting the proliferation, migration, and metastasis of PTC.

Fig. 3

LncRNA and miRNA can decrease mRNA stability or suppress its translation, further influencing the proliferation and metastasis of PTC. A. Upon recognition and binding to the target RNA through its guide RNA (gRNA), Cas13 induces site-specific cleavage of the target RNA molecule. Subsequently, the cleaved RNA fragments are typically degraded by cellular nucleases. B. Upon entry into the target cells, the viral vector introduces the miRNA sequence into the cell's genome. This miRNA sequence is recognized by the cellular transcription machinery and transcribed into miRNA.

Fig. 4

miRNA regulates PTC proliferation, migration, and metastasis. miRNA inhibitors bind to particular miRNA molecules, preventing their complementary interaction with target mRNAs and restoring tumor suppressor protein. This restoration may inhibit PTC proliferation, migration, and metastasis, ultimately contributing to an anti-tumor effect.

Fig. 5

The Wnt/β-catenin signaling pathway potentially contributes to PTC progress. β-catenin is phosphorylated and degraded when the Wnt signal is absent. However, upon activation of the Wnt signal by binding to Frizzled family proteins and its ligand Wnt, the protein tyrosine kinase Dishevelled (Dvl) gets activated, protecting phosphorylated β-catenin from degradation. The β-catenin then enters the nucleus through nuclear pore complexes where it binds with TCF/LEF transcription factors to promote transcription of target genes such as c-Myc and cyclin D1 involved in cellular proliferation.

Fig. 6

The PI3K/Akt signaling pathway induces PTC proliferation. The associated protein initially binds to its cell surface receptor(receptor tyrosine kinases, RTK). RTK activates protein kinases like PI3K, a crucial signaling molecule in cellular growth, proliferation, and migration. Once activated by PI3K, Akt produces phosphatidylinositol-3,4,5-triphosphate (PIP3), a serine/threonine kinase found in cells. Akt is essential in regulating cellular processes, including cell growth, apoptosis, and proliferation through phosphorylation of downstream target proteins(p53/BAD/mTOR/NF-κB), finally promoting PTC proliferation via inhibiting apoptosis and increasing growth.