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

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 (HS) 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.