SND1 Affects Proliferation of Hepatocellular Carcinoma Cell Line SMMC‐7721 by Regulating IGFBP3 Expression

Abstract

Staphylococcal nuclease domain containing 1 (SND1) is a ubiquitously expressed multifunctional protein involved in transcriptional regulation, RNA splicing and RNA metabolism. Ectopic expression of SND1 has been observed in various tumors including colon cancer, breast cancer, prostate cancer and hepatocellular carcinoma (HCC), indicating a positive role of SND1 in tumor initiation and progression. However, the exact role of SND1 in cancers has not been thoroughly investigated. In the present study, we investigated the role of SND1 in HCC. Immunohistochemistry analysis revealed that the expression level of SND1 was higher in HCC tissues than in adjacent nontumor tissues. Stable knockdown of SND1, performed on the HCC cell line SMMC-7721 using shRNA lentiviral expression system, led to reduced cell proliferation, clone formation and tumor formation in nude mice. The insulin-like growth factor (IGF) signaling pathway was frequently dysregulated in HCC, which could facilitate tumor progression. Screening of gene expression levels of the IGF pathway, using real-time PCR, revealed that a decrease in SND1 expression could increase the expression of IGF-binding protein 3 (IGFBP3), which can negatively regulate activation of the IGF pathway by restricting interactions between IGF and IGF receptors. Results from previous studies showed that the downregulation of IGFBP3 expression is Additional Supporting Information may be found in the online version of this article.Jie Yin and Jianmin Ding contributed equally to this work.

Tudor-SN protein expression in colorectal cancer and its association with clinical characteristics

“…In hepatocellular carcinoma, it has been found that 1) SND1 could affect SMMC-7721 cells proliferation by regulating IGFBP3 expression and IGF signaling pathway [20]; 2) SND1 promotes tumor angiogenesis in human hepatocellular carcinoma through pathways that involves nuclear factor κB and miR-221 [21]; and 3) SND1 overexpression deregulates cholesterol homeostasis [22]. Of the few studies that have investigated the role of SND1 in CRC, one paper found that SND1 may contribute to the posttranscriptional regulation of key players in colon cancer development, including APC and β-catenin [18].…”

“…Though SND1 could promote tumor progression through regulating calcium binding proteins, signaling pathways, non-coding RNAs or hormones in different types of other cancer [19][20][21][22], little is known about the exact mechanism of SND1 in CRC. In the present study, we first conducted the SND1 mRNA and protein expression levels https://doi.org/10.1515/biol-2017-0028…”

Tudor staphylococcal nuclease: biochemistry and functions

“…72 Furthermore, TSN could affect hepatocellular carcinoma (HCC) progression by two distinct pathways. 70,73 First, as a member of RISC complex, TSN interacts with AEG-1 leading to the increased degradation of tumor suppressor mRNAs. 70 On the other hand, a negative regulator of insulin-like growth factor (IGF) pathway, an insulinlike growth factor-binding protein 3 (IGFBP3), was reported to be significantly overexpressed in TSN knockdown HCC cells, suggesting the contribution of TSN to cell proliferation, colony and tumor formation.…”

“…70 On the other hand, a negative regulator of insulin-like growth factor (IGF) pathway, an insulinlike growth factor-binding protein 3 (IGFBP3), was reported to be significantly overexpressed in TSN knockdown HCC cells, suggesting the contribution of TSN to cell proliferation, colony and tumor formation. 73 Another important process regulated by TSN is angiogenesis ( Figure 5). TSN promotes angiogenesis in HCC by activating the NF-kB, resulting in the induction of the Figure 4 Role of TSN in the cross-talk between different pathways post-transcriptionally regulating gene expression.…”

The emerging role of astrocyte-elevated gene-1 in hepatocellular carcinoma (Review)

“…SND1 is overexpressed in HCC (85); knockdown of SND1 leads to reduced HCC cell proliferation, clone formation and tumor formation in nude mice (86); and it also regulates HCC angiogenesis by activation of NF-κB and miR-221 inducing angiogenic factors such as angiogenin and CXCL16 (87). The identification of SND1 as an AEG-1-interacting protein was found using two independent approaches, including yeast two hybrid screening using a human liver cDNA library and isolation of AEG-1 interacting proteins by co-immunoprecipitation followed by mass spectrometry.…”