The regulation and interaction of colon cancer‐associated transcript‐1 and miR7‐5p contribute to the inhibition of SP1 expression by solamargine in human nasopharyngeal carcinoma cells

Abstract

Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy with higher incidence in Southern China and Southeast Asia. Solamargine (SM), a steroidal alkaloid glycoside, has been shown to have anticancer properties. However, the underlying mechanism involved remains undetermined. In this study, we showed that SM inhibited the growth of NPC cells. Mechanistically, we found that solamargine decreased lncRNA colon cancer-associated transcript-1 (CCAT1) and increased miR7-5p expression. There was a reciprocal interaction of CCAT1 and miR7-5p. In addition, SM inhibited the expression of SP1 protein and promoter activity, which was strengthened by miR7-5p mimics and inhibited by overexpressed CCAT1.MiR7-5p could bind to 3'-UTR of SP1 and attenuated SP1 gene expression. Exogenously expressed SP1 feedback resisted SM-increased miR7-5p expression and more importantly reversed SM-inhibited growth of NPC cells. Finally, SM inhibited NPC tumor growth in vivo. Collectively, our results show that SM inhibits the growth of NPC cells through reciprocal regulation of CCAT1 and miR7-5p, followed by inhibition of SP1 gene expression in vitro and in vivo. The interregulation and correlation among CCAT1, miR7-5p and SP1, and the feedback regulatory loop unveil the novel molecular mechanism underlying the overall responses of SM in anti-NPC.

A novel three-microRNA signature for predicting survival in patients with nasopharyngeal carcinoma

“… 21 A recent study showed that exogenous SP1 could inhibit the expression of miR7-5p and could reverse the growth of NPC cells inhibited by solamargine. 22 Ho et al. 23 found that melatonin can regulate the expression of matrix metalloprotein 9 (MMP-9) gene induced by tumor promoter 12-o-tetradecanoylphosphate-3-acetate (TPA) by inhibiting the binding ability of SP1 to DNA, thus inhibiting the metastasis activity of NPC.…”

Curaderm, the Long-Awaited Breakthrough for Basal Cell Carcinoma

“…BEC is active against a wide variety of cancer cells, such as ovarian cancer [30], basal cell carcinoma [31], squamous cell carcinoma [32], melanoma [33], colorectal cancer [34], bladder cancer [35], oral epidermoid carcinoma [36], breast cancer [25], leukemia [37], prostate cancer [38], liver cancer [39], lung cancer [40], pancreatic cancer [41], gastric carcinoma [23], renal cancer [31], uterine cancer [30], mesothelioma [42], glioblastoma [43] and osteosarcoma [19]. In addition, BEC has curative properties in animals with terminal cancer [4] [12].…”

Solamargine inhibits the growth of hepatocellular carcinoma and enhances the anticancer effect of sorafenib by regulating HOTTIP‐TUG1/miR‐4726‐5p/MUC1 pathway

“…Solamargine (SM), a natural sugar alkaloid extracted from the fruits of Solanaceae plants, has been fully confirmed by our previous studies and other reports that SM can significantly inhibit the occurrence and development of a variety of cancers. [4][5][6][7] The growing number of studies have found that SM exhibits its antitumor activity through multifarious pathways, including tumor growth pathways, apoptosis-related pathways, mitochondrial pathways, protein kinase pathways, and so on. 8 For example, SM significantly suppresses the expression of X-linked apoptosis inhibitor, PCNA, and cyclin D1, while increasing the activity of caspase-3 to induce apoptosis.…”