DOI: 10.5061/dryad.6t1m4k4
title: Data from: Tumor suppressor RARRES1- a novel regulator of fatty acid metabolism in epithelial cells

description: Retinoic acid receptor responder 1 (RARRES1) is silenced in many cancers
 and is differentially expressed in metabolism associated diseases, such as
 hepatic steatosis, hyperinsulinemia and obesity. Here we report a novel
 function of RARRES1 in metabolic reprogramming of epithelial cells. Using
 non-targeted LC-MS, we discovered that RARRES1 depletion in epithelial
 cells caused a global increase in lipid synthesis. RARRES1-depleted cells
 rewire glucose metabolism by switching from aerobic glycolysis to
 glucose-dependent de novo lipogenesis (DNL). Treatment with fatty acid
 synthase (FASN) inhibitor, C75, reversed the effects of RARRES1 depletion.
 The increased DNL in RARRES1-depleted normal breast and prostate
 epithelial cells proved advantageous to the cells during starvation, as
 the increase in fatty acid availability lead to more oxidized fatty acids
 (FAO), which were used for mitochondrial respiration. Expression of
 RARRES1 in several common solid tumors is also contextually correlated
 with expression of fatty acid metabolism genes and fatty acid-regulated
 transcription factors. Pathway enrichment analysis led us to determine
 that RARRES1 is regulated by peroxisome proliferating activated receptor
 (PPAR) signaling. These findings open up a new avenue for metabolic
 reprogramming and identify RARRES1 as a potential target for cancers and
 other diseases with impaired fatty acid metabolism.
description: RARRES1 Co-expression
 DataOncomineTM (Compendia
 Bioscience, Ann Arbor, MI, USA) was used to identify cancers where RARRES1
 gene expression was significantly upregulated or downregulated. These
 cancers included breast, cervical, colorectal, esophageal, gastric, head
 and neck, kidney, liver, lung, lymphoma, pancreatic and prostate (S1 Table
 from OncomineTM). Of the identified cancers, three (breast, colorectal and
 prostate) were selected for further analysis given the number of datasets
 found to have significant RARRES1 gene expression changes as well as the
 literature known about RARRES1 and its molecular biology within these
 cancers. Within the cancers selected, individual datasets were chosen
 given their large sample sizes and subtype analyses. Thus, The Cancer
 Genome Atlas (TCGA) Breast Cancer, TCGA Colorectal Cancer, and Grasso
 Prostate datasets were selected. The Grasso Prostate dataset was also
 uniquely selected for its metastatic vs. primary analysis (21). For the
 TCGA Breast Cancer dataset, subtype analysis was stratified into ER+ vs.
 ER- status; PR+ vs. PR- status and Triple Negative (PR-, HER2- & ER-)
 vs. non-Triple Negative (22). Metastatic vs. primary site analysis was
 performed in the Grasso Prostate dataset. All colorectal cancer types
 (rectal mucinous adenocarcinoma, colon adenocarcinoma, rectal
 adenocarcinoma, colon mucinous adenocarcinoma and cecum adenocarcinoma)
 identified in the TCGA dataset were also analyzed in comparison to their
 respective normal samples (S1 File) (23). Genes positively or negatively
 co-expressed with RARRES1 were further identified using OncomineTM with
 respect to each dataset of tumor vs. normal.Supplementary Information_Supp.
 File 1 (1).xlsxGC-MS Raw Data (RARRES1
 siRNA)CSV files and raw data
 files are included in the zip file. RARRES1 siRNA and scrambled siRNA
 samples were run.GC-MS.zipSample Annotations for GC-MS and LC-MS RunsDescription of runs and sample annotations for GC-MS and LC-MS are included.Sample Annotations for LCMS and GCMS.zipLC-MS Raw Data RARRES1 KD (1) (xaa)We split the LC-MS raw data using the "Split" Linux function into 4 files (combine using "cat xaa xab ... &gt; lcms.zip")xaaLC-MS Raw Data RARRES1 KD (2) (xab)We split the LC-MS raw data using the "Split" Linux function into 17 files (combine using "cat xaa xab ... &gt; lcms.zip")xabLC-MS Raw Data RARRES1 KD (3) (xac)We split the LC-MS raw data using the "Split" Linux function into 17 files (combine using "cat xaa xab ... &gt; lcms.zip")xacLC-MS Raw Data RARRES1 KD (4) (xad)We split the LC-MS raw data using the "Split" Linux function into 17 files (combine using "cat xaa xab ... &gt; lcms.zip")xadLC-MS Raw Data RARRES1 KD (5) (xae)We split the LC-MS raw data using the "Split" Linux function into 17 files (combine using "cat xaa xab ... &gt; lcms.zip")xaeLC-MS Raw Data RARRES1 KD (7) (xaf)We split the LC-MS raw data using the "Split" Linux function into 17 files (combine using "cat xaa xab ... &gt; lcms.zip")xafLC-MS Raw Data RARRES1 KD (7) (xag)We split the LC-MS raw data using the "Split" Linux function into 17 files (combine using "cat xaa xab ... &gt; lcms.zip")xagLC-MS Raw Data RARRES1 KD (8) (xah)We split the LC-MS raw data using the "Split" Linux function into 17 files (combine using "cat xaa xab ... &gt; lcms.zip")xahLC-MS Raw Data RARRES1 KD (9) (xai)We split the LC-MS raw data using the "Split" Linux function into 17 files (combine using "cat xaa xab ... &gt; lcms.zip")xaiLC-MS Raw Data RARRES1 KD (10) (xaj)We split the LC-MS raw data using the "Split" Linux function into 17 files (combine using "cat xaa xab ... &gt; lcms.zip")xajLC-MS Raw Data RARRES1 KD (11) (xaK)We split the LC-MS raw data using the "Split" Linux function into 17 files (combine using "cat xaa xab ... &gt; lcms.zip")xakLC-MS Raw Data RARRES1 KD (12) (xaL)We split the LC-MS raw data using the "Split" Linux function into 17 files (combine using "cat xaa xab ... &gt; lcms.zip"xalLC-MS Raw Data RARRES1 KD (13) (xaM)We split the LC-MS raw data using the "Split" Linux function into 17 files (combine using "cat xaa xab ... &gt; lcms.zip")xamLC-MS Raw Data RARRES1 KD (14) (xaN)We split the LC-MS raw data using the "Split" Linux function into 17 files (combine using "cat xaa xab ... &gt; lcms.zip")xanLC-MS Raw Data RARRES1 KD (14) (xao)We split the LC-MS raw data using the "Split" Linux function into 17 files (combine using "cat xaa xab ... &gt; lcms.zip")xaoLC-MS Raw Data RARRES1 KD (16) (xap)We split the LC-MS raw data using the "Split" Linux function into 17 files (combine using "cat xaa xab ... &gt; lcms.zip")xapLC-MS Raw Data RARRES1 KD (17) (xaq)We split the LC-MS raw data using the "Split" Linux function into 17 files (combine using "cat xaa xab ... &gt; lcms.zip")xaq