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SIDT2 RNA Transporter Promotes Lung and Gastrointestinal Tumor Development.


ABSTRACT: RNautophagy is a newly described type of selective autophagy whereby cellular RNAs are transported into lysosomes for degradation. This process involves the transmembrane protein SIDT2, which transports double-stranded RNA (dsRNA) across the endolysosomal membrane. We previously demonstrated that SIDT2 is a transcriptional target of p53, but its role in tumorigenesis, if any, is unclear. Unexpectedly, we show here that Sidt2-/- mice with concurrent oncogenic KrasG12D activation develop significantly fewer tumors than littermate controls in a mouse model of lung adenocarcinoma. Consistent with this observation, loss of SIDT2 also leads to enhanced survival and delayed tumor development in an Apcmin/+ mouse model of intestinal cancer. Within the intestine, Apcmin/+;Sidt2-/- mice display accumulation of dsRNA in association with increased phosphorylation of eIF2α and JNK as well as elevated rates of apoptosis. Taken together, our data demonstrate a role for SIDT2, and by extension RNautophagy, in promoting tumor development.

SUBMITTER: Nguyen TA 

PROVIDER: S-EPMC6817685 | biostudies-other | 2019 Oct

REPOSITORIES: biostudies-other

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SIDT2 RNA Transporter Promotes Lung and Gastrointestinal Tumor Development.

Nguyen Tan A TA   Bieging-Rolett Kathryn T KT   Putoczki Tracy L TL   Wicks Ian P IP   Attardi Laura D LD   Pang Ken C KC  

iScience 20190910


RNautophagy is a newly described type of selective autophagy whereby cellular RNAs are transported into lysosomes for degradation. This process involves the transmembrane protein SIDT2, which transports double-stranded RNA (dsRNA) across the endolysosomal membrane. We previously demonstrated that SIDT2 is a transcriptional target of p53, but its role in tumorigenesis, if any, is unclear. Unexpectedly, we show here that Sidt2<sup>-/-</sup> mice with concurrent oncogenic Kras<sup>G12D</sup> activa  ...[more]

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