RASSF10 is Epigenetically Inactivated and Suppresses Cell Proliferation and Induces Cell Apoptosis by Activating the p53 Signalling Pathway in Papillary Thyroid Carcinoma Cancer

Abstract

Objectives: We aimed to confirm whether RASSF10 activated the p53 signalling pathway, thereby modulating cell proliferation, migration, invasion, and apoptosis in papillary thyroid carcinoma (PTC) cells. Methods: A total of 108 PTC tissue samples and normal adjacent tissues were obtained. RT-PCR and Western blotting analyses were performed to detect RASSF10 expression, and methylation levels of RASSF10 were estimated by methylation-specific PCR (MSP). We also detected the expression and methylation status of RASSF10 in both a human PTC cell line (K1) and a normal thyroid cell line (FRTL5). After transfection of cells with empty vector pcDNA3.1, pcDNA3.1-RASSF10, p53 siRNA and shRASSF10, Coulter counter, colony-formation, wound healing, Transwell and flow cytometry analyses were performed to examine the role of RASSF10 in cell proliferation, migration, invasion, and apoptosis. Finally, the expression of p53, p21, Bcl-2 and Bax were detected using Western Blotting analyses. Results: RASSF10 expression in PTC tissues was significantly lower and hyper-methylated compared to normal adjacent tissues. In addition, RASSF10 was significantly down-regulated and hyper-methylated in K1 cells compared to FRTL5 cells. In addition, suppressed proliferation and significantly induced apoptosis of K1 cells were observed after transfection with pcDNA3.1-RASSF10 (P < 0.05). Furthermore, RASSF10 activated the p53 signalling pathway and regulated the expression of p53, p21, Bcl-2 and Bax. Furthermore, p53 siRNA could antagonize the effects of RASSF10 in K1 cells. Conclusions: RASSF10 induces apoptosis in PTC cells by activating the p53 signalling pathway, indicating its role as a treatment target for PTC.

I-BET726 suppresses human skin squamous cell carcinoma cell growth in vitro and in vivo

“…Following I-BET726 treatment, A431 cells were placed onto 10-cm dishes (2×10 4 cells per treatment) 10 . I-BET726 medium was renewed every two days.…”

RASSF10 is frequently epigenetically inactivated in kidney cancer and its knockout promotes neoplasia in cancer prone mice

“…We showed the epigenetic inactivation of RASSF10 in breast cancer [26], lung cancer [20], skin cancer [27], and thyroid cancer [21] and showed that RASSF10 inhibited the growth of breast cancer [26], pancreas carcinoma, and sarcoma cell lines [20]. So far, RASSF10 has only been studied in vitro and inconsistent pathways of action were suggested like cAMP-PKA signaling [20], MMP2 [28], p53 [29], and JNK [30]. In vivo analyses of RASSF10 were missing and the function of RASSF10 has not been analyzed in kidney cancer.…”

RASSF10 Is a TGFβ-Target That Regulates ASPP2 and E-Cadherin Expression and Acts as Tumor Suppressor That Is Epigenetically Downregulated in Advanced Cancer

“…Epigenetic inactivation of RASSF10 through promoter hypermethylation has been reported in various tumor entities including lung cancer, thyroid cancer, melanoma and several others [17][18][19][20][21][22]. Functional studies have shown that RASSF10 signaling is linked to the cAMP-PKA (Protein kinase A) pathway [19], MMP2 (Matrix metallopeptidase 2) [23], p53 [24] or JNK (c-Jun N-terminale kinase) pathway [25].…”