Date

2021-11-01

Author

Erson Bensan, Ayşe Elif
Özgül, İbrahim
Erdem, Murat
Döken, Didem Naz

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Roles of HNRNPA1 are beginning to emerge in cancers; however, mechanisms causing deregulation of HNRNPA1 function remain elusive. Here, we identify and characterize an isoform switch between the 3’-UTR isoforms of HNRNPA1. We show that the dominantly expressed isoform in mammary tissue has a short half-life. In breast cancers, this isoform is downregulated, whereas a stable isoform is expressed more. As a result, the HNRNPA1 protein is upregulated. High HNRNPA1 protein levels correlate with poor survival in patients. In support of an oncogenic role, silencing of HNRNPA1 causes a reversal in neoplastic phenotypes, including proliferation, clonogenic potential, Hypercholesterolemia is considered as a risk factor for various cancers, including colorectal cancer (CRC). With the increasing population of hypercholesterolemic individuals (39% globally, WHO), the importance of understanding the role of cholesterol in cancer cell proliferation is very much needed. In majorities of cancer, lipid or cholesterol metabolism are dysregulated to supports rapid cell proliferation. Moreover, pre-clinical and clinical findings also reported an abnormality in the blood cholesterol level of CRC patients. In this study, we explored the relevance of cholesterol-induced altered glucose metabolism in CRC and its involvement in proliferation. Human low-density lipoprotein cholesterol (LDLc) or high-density lipoprotein cholesterol (HDLc) were used to investigate their effect on CRC cells proliferation through various cell base studies, including seahorse analysis for glycolysis, oxidative phosphorylation (OXPHOS), and ATP rate assay through real-time analysis of oxygen consumption rate (OCR) or extracellular acidification migration, and invasion. In addition, silencing of HNRNPA1 results in the downregulation of microRNAs that map to intragenic regions. Among these miRNAs, miR-21 is known as an oncogene in breast and numerous other cancers. Overall, the cancer-specific isoform switch we describe here for HNRNPA1 exemplifies an oncogene activation case in breast cancers. our data emphasize that focusing on isoform level changes is essential to decoding the cancer transcriptome in higher resolution. This perspective may allow the identification of new oncogene activation cases where overall mRNA levels may not change significantly, or common driver mutations do not exist at the genome level.

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https://files-myxp.gevme.com/VRtpg0Q1JTvbcqaetKVNf9aSt/61515a2cfc5c07004568113b/O9WvS/fcs%202021%20abstract%20book_scroll.pdf
https://hdl.handle.net/11511/94520

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Department of Biology, Conference / Seminar