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PreprintCC BY-NC-NDbioRxiv

KSHV upregulates the long non-coding RNA PURPL via p73 to suppress p53

  1. 1Azrieli Faculty of Medicine in the Galilee, Bar-Ilan University

Abstract

Long non-coding RNAs (lncRNAs) are a class of regulatory RNAs with lengths exceeding 200 nucleotides. The lncRNA PURPL (p53 upregulated regulator of p53 levels) is a p53-regulated gene. PURPL is an oncogenic lncRNA that represses p53 function; it is upregulated in many tumors and promotes cancer cell proliferation. Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of all forms of Kaposi sarcoma (KS) and is tightly associated with primary effusion lymphoma (PEL). We found upregulation of PURPL in both de novo and chronically KSHV-infected cells. We found that p73 (a p53 homolog) associates with the PURPL promoter and upregulates PURPL expression. Previously, it has been shown that KSHV-encoded latency-associated nuclear antigen (LANA) stabilizes p73. We found that ectopic expression of LANA increased both p73 protein levels and PURPL expression. p73 knockdown abrogates PURPL upregulation following KSHV infection. Antisense oligonucleotides (ASO) targeting PURPL reduced PEL cell proliferation and increased acetylated p53 levels. In contrast to p53, p73 is not repressed by PURPL RNA. In summary, our study reveals how an oncogenic virus can utilize p73 to upregulate the oncogenic lncRNA PURPL as an additional way to repress p53. Moreover, we propose another mechanism by which p73 may promote tumor growth.

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BibTeX
@misc{showgan2026kshv,
  title = {{KSHV upregulates the long non-coding RNA PURPL via p73 to suppress p53}},
  author = {S. Showgan and D. Meary and G. Journo and V. Gurevich and M. Shamay},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.02.755609},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.02.755609v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - KSHV upregulates the long non-coding RNA PURPL via p73 to suppress p53
AU  - S. Showgan
AU  - D. Meary
AU  - G. Journo
AU  - V. Gurevich
AU  - M. Shamay
PY  - 2026
DA  - 2026/10/02
PB  - bioRxiv
DO  - 10.64898/2026.10.02.755609
UR  - https://www.biorxiv.org/content/10.64898/2026.10.02.755609v1
AB  - Long non-coding RNAs (lncRNAs) are a class of regulatory RNAs with lengths exceeding 200 nucleotides. The lncRNA PURPL (p53 upregulated regulator of p53 levels) is a p53-regulated gene. PURPL is an oncogenic lncRNA that represses p53 function; it is upregulated in many tumors and promotes cancer cell proliferation. Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of all forms of Kaposi sarcoma (KS) and is tightly associated with primary effusion lymphoma (PEL). We found upregulation of PURPL in both de novo and chronically KSHV-infected cells. We found that p73 (a p53 homolog) associates with the PURPL promoter and upregulates PURPL expression. Previously, it has been shown that KSHV-encoded latency-associated nuclear antigen (LANA) stabilizes p73. We found that ectopic expression of LANA increased both p73 protein levels and PURPL expression. p73 knockdown abrogates PURPL upregulation following KSHV infection. Antisense oligonucleotides (ASO) targeting PURPL reduced PEL cell proliferation and increased acetylated p53 levels. In contrast to p53, p73 is not repressed by PURPL RNA. In summary, our study reveals how an oncogenic virus can utilize p73 to upregulate the oncogenic lncRNA PURPL as an additional way to repress p53. Moreover, we propose another mechanism by which p73 may promote tumor growth.
ER  -