CRISPR/Cas9 Screen Uncovers Functional Translation of Cryptic lncRNA-Encoded Open Reading Frames in Human Cancer

Emerging evidence suggests that cryptic translation within long noncoding RNAs (lncRNAs) may produce novel proteins with important developmental/physiological functions. However, the role of this cryptic translation in complex diseases (e.g., cancer) remains elusive. Here, we applied an integrative strategy combining ribosome profiling and CRISPR/Cas9 screening with large-scale analysis of molecular/clinical data for breast cancer (BC) and identified estrogen receptor α-positive (ER+) BC dependency on the cryptic ORFs encoded by lncRNA genes that were upregulated in luminal tumors. We confirmed the in vivo tumor-promoting function of an unannotated protein, GATA3-interacting cryptic protein (GT3-INCP) encoded by LINC00992, the expression of which was associated with poor prognosis in luminal tumors. GTE-INCP was upregulated by estrogen/ER and regulated estrogen-dependent cell growth. Mechanistically, GT3-INCP interacted with GATA3, a master transcription factor key to mammary gland development/BC cell proliferation, and coregulated a gene expression program that involved many BC susceptibility/risk genes and impacted estrogen response/cell proliferation. GT3-INCP/GATA3 bound to common cis regulatory elements and upregulated the expression of the tumor-promoting and estrogen-regulated BC susceptibility/risk genes MYB and PDZK1. Our study indicates that cryptic lncRNA-encoded proteins can be an important integrated component of the master transcriptional regulatory network driving aberrant transcription in cancer, and suggests that the hidden lncRNA-encoded proteome might be a new space for therapeutic target discovery

Migration and arsenic adsorption study of starch-modified Fe-Ce oxide on a silicon-based micromodel observation platform

Iron materials have shown great potential to remediate arsenic (As) contaminated sites. It's very important to reveal the reaction process between iron materials and As from the perspective of pore scale, but relevant research was inadequate. In order to directly investigate the migration and As adsorption mechanism of starch-modified Fe-Ce oxide in pore scale, a silicon-based micromodel observation platform was established in this study. The results of Charge coupled Device images showed that the sedimentation surface area of SFC occupied about 57.02% of the large porosity zone, but only 23.27% of the small porosity zone. To further reveal the 3D distribution of Fe and As elements inside the pore network, Laser Induced Breakdown Spectroscopy was introduced. The results revealed that less As was adsorbed as less SFC intruded in the small porosity zone. When the large porosity zone was blocked by SFC, a permeability barrier was created to adsorb As from upstream. This study also explored the effect of particle size reduction on SFC migration, and found it might be a better candidate for more SFC penetrated into small porosity zone. Combined with various high-resolution and sensitivity-detection methodologies, more colloidal migration mechanisms can be investigated using this technology in the future. (C) 2017 Elsevier B.V. All rights reserved.National Natural Science Foundation of China [41571309]; National High Technology Research and Development Program of China (863 Program) [2013AA06A206]; National Nature Science Foundation of China [41271339]SCI(E)ARTICLE202-20733