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Upregulation of LHPP by saRNA inhibited hepatocellular cancer cell proliferation and xenograft tumor growth.
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- معلومة اضافية
- المصدر:
Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
- بيانات النشر:
Original Publication: San Francisco, CA : Public Library of Science
- الموضوع:
- نبذة مختصرة :
Hepatocellular carcinoma (HCC) is the most common primary liver cancer worldwide and no pharmacological treatment is available that can achieve complete remission of HCC. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a recently identified HCC tumor suppressor gene which plays an important role in the development of HCC and its inactivation and reactivation has been shown to result in respectively HCC tumorigenesis and suppression. Small activating RNAs (saRNAs) have been used to achieve targeted activation of therapeutic genes for the restoration of their encoded protein through the RNAa mechanism. Here we designed and validated saRNAs that could activate LHPP expression at both the mRNA and protein levels in HCC cells. Activation of LHPP by its saRNAs led to the suppression of HCC proliferation, migration and the inhibition of Akt phosphorylation. When combined with targeted anticancer drugs (e.g., regorafenib), LHPP saRNA exhibited synergistic effect in inhibiting in vitro HCC proliferation and in vivo antitumor growth in a xenograft HCC model. Findings from this study provides further evidence for a tumor suppressor role of LHPP and potential therapeutic value of restoring the expression of LHPP by saRNA for the treatment of HCC.
Competing Interests: TK, MK and L-CL are employees of Ractigen Therapeutics and named inventors of a patent application which is based on part of this work. Patent number: US20220096516A1; Patent name: Oligonucleotide molecule and application thereof in tumor therapy. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
(Copyright: © 2024 Bi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- الرقم المعرف:
EC 3.6.1.1 (Inorganic Pyrophosphatase)
EC 3.6.1.1 (phospholysine phosphohistidine inorganic pyrophosphate phosphatase, human)
- الموضوع:
Date Created: 20240502 Date Completed: 20240502 Latest Revision: 20240521
- الموضوع:
20240521
- الرقم المعرف:
PMC11065268
- الرقم المعرف:
10.1371/journal.pone.0299522
- الرقم المعرف:
38696452
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