Role of the staphylococcal nuclease and tudor domain containing 1 in oncogenesis (Review)

Abstract

The staphylococcal nuclease and tudor domain containing 1 (SND1) is a multifunctional protein overexpressed in breast, prostate, colorectal and hepatocellular carcinomas and malignant glioma. Molecular studies have revealed the multifaceted activities of SND1 involved in regulating gene expression at transcriptional as well as post-transcriptional levels. Early studies identified SND1 as a transcriptional co-activator. SND1 is also a component of RNA-induced silencing complex (RISC) thus mediating RNAi function, a regulator of mRNA splicing, editing and stability, and plays a role in maintenance of cell viability. Such diverse actions allow the SND1 to modulate a complex array of molecular networks, thereby promoting carcinogenesis. Here, we describe the crucial role of SND1 in cancer development and progression, and highlight SND1 as a potential target for therapeutic intervention.

Oncogenic Role of SND1 in Development and Progression of Hepatocellular Carcinoma

“…SND1 interacts with monoglyceride lipase (MGLL) resulting in MGLL degradation which leads to activation of Akt and stimulation of cell proliferation and cell cycle progression in HCC cells (17). Overall, SND1 plays a dynamic role in regulating expression of genes crucial to hepatocarcinogenesis by employing diverse transcriptional as well as post-transcriptional molecular mechanisms (15,18). …”

“…However, whether the other functions of SND1 require enzymatic activity remains to be determined. Structurally, SND1 is unique in the human proteome with no close homolog as revealed by BLAST search (18). The closest homolog of SND1 is EBNA2, which is not transcribed.…”

The multifaceted oncogene SND1 in cancer: focus on hepatocellular carcinoma

“…Transcriptional activation of oncogenes, over-expression of oncogenic splice variants through alternative splicing, degradation of tumor suppressor proteins and silencing of tumor suppressor mRNAs are some of the means used by SND1 to contribute to tumorigenesis [ Figure 2]. Given its role in regulating a wide variety of cellular properties, it comes as no surprise that SND1 functions as an oncogene in a variety of cancers, including breast, liver, lung, gastric, glial, prostate and colorectal cancer [25] . Although the molecular mechanism by which SND1 is overexpressed in cancer is not clear, it has been identified as a target of a number of tumor suppressor miRNAs, such as microRNA-320a in lung cancer [31] , microRNA-361-5p in colorectal and gastric cancer [32] , and miRNA-184 in malignant glioma [33] [ Figure 1B].…”

“…SND1 is involved in regulating gene expression by transcriptional activation [18][19][20] , alternative splicing [21] , ubiquitination [17] , mRNA stabilization [22] and RNA interference [23] . These multifaceted properties allow SND1 to positively impact all hallmarks of cancer, notably sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis [24,25] .…”

Tudor-SN–mediated endonucleolytic decay of human cell microRNAs promotes G 1 /S phase transition

“…S22H). Thus, TSN KD disrupts the tight control of mRNAs encoding cell-cycle regulatory proteins via TumiD, offering an explanation for the elevated levels of TSN that can typify rapidly proliferating cells (19). …”