PMID:28275056

Citation	'Bikkavilli, RK, Zerayesus, SA, Van Scoyk, M, Wilson, L, Wu, PY, Baskaran, A, Tang, K, Raheem, S, Samuelson, BA, Reddy, NM, Reddy, SP, Cool, CD, Kosmider, B, Avasarala, S and Winn, RA (2017) KSRP promotes post-transcriptional destabilization of Spry4 transcripts in non-small cell lung cancer. J. Biol. Chem. '
Abstract	AU-rich element binding proteins (ARE-BPs) offer post-transcriptional regulation of gene expression via physical interaction and recruitment of RNA decay machinery to the AU-rich elements within the 3'UTR of the target transcripts. However, the role of ARE-BPs in lung cancer remains poorly understood. In this study, we have identified that K-homology splicing regulatory protein (KSRP), an ARE-BP, is robustly up-regulated in human lung cancer. Importantly, Kaplan-Meier survival analysis indicated that elevated KSRP expression was correlated with poor overall survival of lung cancer patients. Furthermore, cigarette smoke, a leading risk factor for lung cancer, was also identified to be an important contributor to increased KSRP expression. Remarkably, silencing of KSRP decreased cell proliferation, reversed anchorage-independent growth, and reduced migration/invasion, suggesting an oncogenic role for KSRP in lung cancer. Finally, we provide a mechanistic evidence that KSRP promotes the down regulation of Spry4 by a previously unidentified mechanism i.e., post-transcriptional mRNA regulation.
Links	PubMed Online version:10.1074/jbc.M116.757906
Keywords
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:FUBP2		GO:0008284: positive regulation of cell proliferation	ECO:0000315:		P		Organism: Homo sapiens. Paper’s Protein Name: K homology splicing regulatory protein (KSRP). UniProt’s Protein Name: Far upstream element-binding protein 2 OR ALTERNATIVELY KH type-splicing regulatory protein. Notes: Figures 2C-D are primarily used, but Figures 2A-B help to understand the resuls. This is because Figures 2A-B show that “Transfection of H2122 and H157 with two different KSRP specific siRNAs resulted in a significant reduction of KSRP expression.” Thus, when Figures 2C-D show that the “knockdown conditions” created by these siRNAs lead to decreased cellular proliferation over time, it is clear that KSRP is linked to cellular proliferation. No UniProt term appears to be specific to the non-small cell lung cancer cell line.	complete CACAO 12361
HUMAN:FUBP2		GO:0030335: positive regulation of cell migration	ECO:0000315:		P		Organism: Homo sapiens Paper’s Protein Name: K homology splicing regulatory protein (KSRP). UniProt’s Protein Name: Far upstream element-binding protein 2 OR ALTERNATIVELY KH type-splicing regulatory protein. Notes: Figure 3E is used. According to the paper, “the stable knockdown of KSRP resulted in reduced cell migration, when compared to H2122 clones stably expressing control shRNAs.” In other words, decreased levels of KSRP are linked to decreased levels of cellular migration. No UniProt term appears to be specific to the non-small cell lung cancer cell line.	complete CACAO 12363
HUMAN:FUBP2		GO:0061158: 3'-UTR-mediated mRNA destabilization	ECO:0000315:		P		Paper’s Protein Name: K homology splicing regulatory protein (KSRP). UniProt’s Protein Name: Far upstream element-binding protein 2 OR ALTERNATIVELY KH type-splicing regulatory protein. Organism: Homo sapiens. Notes: Figure 6E is used. Figure 4 had already demonstrated that KSRP downregulates the Spry4 protein, and Figure 5D had already demonstrated that KSRP binds to the 3’-UTR mRNA of the Spry4 gene. In the paper, it is claimed that “if the effects of KSRP on Spry4 3’UTR were specific; then upon KSRP knockdown, the KSRP-mediated mRNA repression should be relaxed, as detected by an increase in luciferase activities. Indeed, knockdown of KSRP increased the luciferase activities of Luc-Spry4 UTR, but not the luciferase activities of Luc-Spry4 UTR-F1.” The chart in Figure 6E does indeed show that luciferase activities approximately double when KSRP is mutated. Thus, KSRP destabilizes the mRNA of Spry4 by binding to the 3’-UTR region.	complete CACAO 12364

References

See Help:References for how to manage references in GONUTS.