Healthy Research Rewards
ResearchHub is incentivizing healthy research behavior. At this time, first authors of open access papers are eligible for rewards. Visit the publications tab to view your eligible publications.
Got it
JD
Janne Darell
Author with expertise in Human Papillomavirus and Cervical Cancer Epidemiology
Achievements
Open Access Advocate
Key Stats
Upvotes received:
0
Publications:
1
(100% Open Access)
Cited by:
0
h-index:
0
/
i10-index:
0
Reputation
Biology
< 1%
Chemistry
< 1%
Economics
< 1%
Show more
How is this calculated?
Publications
0

E7-mediated repression of miR-203 promotes LASP1-dependent proliferation in HPV-positive cervical cancer

Molly Patterson et al.May 24, 2024
Abstract Human papillomaviruses (HPV) are a major cause of malignancy, contributing to ~5% of all human cancers worldwide, including most cervical cancer cases and a growing number of anogenital and oral cancers. The major HPV viral oncogenes, E6 and E7, manipulate many host cellular pathways that promote cell proliferation and survival, predisposing infected cells to malignant transformation. Despite the availability of highly effective vaccines, there are still no specific anti-viral therapies targeting HPV or treatments for HPV-associated cancers. As such, a better understanding of viral-host interactions may allow the identification of novel therapeutic targets. Here, we demonstrate that the actin-binding protein LASP1 is upregulated in cervical cancer and significantly correlates with a poorer overall survival. In HPV positive cervical cancer, LASP1 depletion significantly inhibited the oncogenic phenotype in vitro, whilst having minimal effects in HPV negative cervical cancer cells. Furthermore, we demonstrate that the LASP1 SH3 domain is essential for LASP1-mediated oncogenicity in these cells. Mechanistically, we show that HPV E7 regulates LASP1 at the post-transcriptional level by repressing the expression of miR-203, which negatively regulates LASP1 mRNA levels by binding to its 3’UTR. Finally, we demonstrate that LASP1 expression is required for the growth of HPV positive cervical cancer cells in an in vivo tumourigenicity model. Together, these data demonstrate that HPV induces LASP1 expression to promote proliferation and survival in cervical cancer, thus identifying a potential therapeutic target in these cancers.