In colonic ρ0 (rho0) cells reduced mitochondrial function mediates transcriptomic alterations associated with cancer

Harrison M. Penrose1,*, Sandra Heller1,*, Chloe Cable1, Hani Nakhoul1, Nate Ungerleider1, Melody Baddoo1, Zachary F. Pursell2, Erik K. Flemington1, Susan E. Crawford3, Suzana D. Savkovic1

1 Department of Pathology and Laboratory Medicine, Tulane University, New Orleans, LA 70112, USA

2 Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, New Orleans, LA 70112, USA

3 Department of Surgery, NorthShore, Research Institute, Affiliate of University of Chicago Pritzker School of Medicine, Evanston, IL 60201, USA

* These authors contributed equally to this work

Correspondence to:

Suzana D. Savkovic, email: ssavkovi@tulane.edu

Keywords: colon cancer, mitochondria, p0 (rho0) cells, transcriptome

Received: September 06, 2017 Accepted: November 11, 2017 Published: December 27, 2017


Background: Mitochondrial reprograming has emerged as a hallmark of cancer pathobiology. Although it is believed this reprogramming is essential for cancer cells to thrive, how it supports cancer pathobiology is unclear. We previously generated colonic p0 (rho0) cells with reduced mitochondrial energy function and acquired their transcriptional signature. Here, we utilized a bioinformatics approach to identify their changes linked to cancer pathobiology. Methods: Human colon cancer HCT116 cells, control and p0, were used for qPCR. Bioinformatics analysis: GeneCards, Kaplan-Meier Survival, GENT, cBioPortal. Results: The colonic p0 transcriptome was linked with proliferation, DNA replication, survival, tumor morphology, and cancer. Among differentially expressed transcripts, 281 were regulators or biomarkers of human colon cancer especially those with inflammatory microsatellite instability (MSI). We identified and validated novel transcripts in p0 cells with altered expression in human colon cancer. Among them, DGK1, HTR7, FLRT3, and ZBTB18 co-occurred with established regulators of human colon cancer pathobiology. Also, increased levels of DGKI, FLRT3, ZBTB18, and YPEL1 as well as decreased levels of HTR7, and CALML6 were linked to substantially poorer patient survival. Conclusion: We identified established and novel regulators in colon cancer pathobiology that are dependent on mitochondrial energy reprogramming and linked to poorer patient survival.

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