Melatonin promotes apoptosis of thyroid cancer cells via regulating the signaling of microRNA-21 (miR-21) and microRNA-30e (miR-30e)

Abstract

Melatonin (MEL) is an effective therapeutic choice for thyroid cancer treatment. In this study, we aimed to explored the potential effect of MEL upon the drug sensitivity of cancer cells and the according underlying mechanisms. Thyroid cancer mice were established as a control group and a MEL group to observe the in vivo effect of MEL. Tumor size and weight in nude mice were detected to evaluate the effect of MEL on tumor growth. Immunohistochemistry assay (IHC) and Western blot were performed to analyze the expression of PTEN protein in tumor cells or tumor cells. After 32 days of cancer cell implantation, MEL was found to significantly repress tumor growth in nude mice approximately by half. Moreover, MEL also suppressed tumor cell proliferation, while apparently activating the apoptosis of tumor cells. In addition, hydrogen sulfide (H 2 S) production was obviously elevated by MEL treatment. Mechanistically, the expression of phosphatase and tensin homolog (PTEN) was remarkably activated by MEL treatment in tumor tissues of implanted TPC-1 and BCPaP cells in nude mice. Meanwhile, MEL inhibited the expression of miR-21 and miR-30e and promoted the expression of lncRNA-cancer susceptibility candidate 7 (CASC7). Both miR-21 and miR-30e could suppress PTEN expression, while miR-21 could also inhibit the expression of lncRNA-CASC7. In conclusion, the results demonstrated that the MEL administration could downregulate the expression of miR-21 and miR-30e, which resulted in increased expression of PTEN, a pro-apoptotic tumor suppressor, to promote the apoptosis of thyroid cancer cells.

Advances in targeted therapy and biomarker research in thyroid cancer

“…miR-146b is known for its ability to modulate inflammation, and it is frequently downregulated in PTC ( 63 ). The miR-221/222 cluster is often overexpressed in thyroid cancer and has a role in controlling important signaling pathways that support the growth and survival of cells ( 64 ). Thyroid cancer is associated with an upregulation of miR-155, which facilitates the migration and proliferation of cancer cells ( 65 ).…”

“…MiRNA expression profiles function as predictive and diagnostic indicators. Preoperative diagnosis accuracy can be improved by using specific miRNA signatures that can distinguish between benign and malignant thyroid lesions ( 62 – 64 ). MiRNA expression patterns have a wide range of potential therapeutic applications.…”

“…MiRNA expression patterns have a wide range of potential therapeutic applications. To restore or suppress certain miRNAs for therapeutic purposes, researchers are investigating the creation of miRNA-based therapies, such as miRNA mimics and inhibitors ( 62 – 64 ). Technological developments like microarray studies and high-throughput sequencing have made it possible to profile miRNAs in a wide range of biological samples ( 62 – 64 ).…”

“…To restore or suppress certain miRNAs for therapeutic purposes, researchers are investigating the creation of miRNA-based therapies, such as miRNA mimics and inhibitors ( 62 – 64 ). Technological developments like microarray studies and high-throughput sequencing have made it possible to profile miRNAs in a wide range of biological samples ( 62 – 64 ). These methods enable researchers to find important regulatory networks, discover patterns of global miRNA expression, and locate putative illness biomarkers ( 62 – 64 ).…”

“…Technological developments like microarray studies and high-throughput sequencing have made it possible to profile miRNAs in a wide range of biological samples ( 62 – 64 ). These methods enable researchers to find important regulatory networks, discover patterns of global miRNA expression, and locate putative illness biomarkers ( 62 – 64 ). MiRNA expression profiles provide a complex layer of biological data that aids our knowledge of thyroid cancer and other disorders ( 62 – 65 ).…”