Specific inhibition of FGF5-induced cell proliferation by RNA aptamers

Amano, R. S.; Namekata, Masato; Horiuchi, Masataka; Saso, Minami; Yanagisawa, Takuya; Tanaka, Yoichiro; Ghani, Farhana Ishrat; Yamamoto, Masakuni; Sakamoto, Taiichi

doi:10.1038/s41598-021-82350-w

Cited by 16 publications

(7 citation statements)

References 39 publications

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“…An RNA aptamer that binds FGF5 with high affinity was shown to inhibit FGF5‐induced cell proliferation, but not FGF2‐induced cell proliferation. As mutations or knockout of Fgf5 results in abnormally long hair, this aptamer may be useful to enhance hair growth (Amano et al, 2021; Hébert et al, 1994).…”

Section: Development Of Fgf Pathway Inhibitors As Pharmaceuticalsmentioning

confidence: 99%

New developments in the biology of fibroblast growth factors

Ornitz

Itoh

2022

WIREs Mechanisms of Disease

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The fibroblast growth factor (FGF) family is composed of 18 secreted signaling proteins consisting of canonical FGFs and endocrine FGFs that activate four receptor tyrosine kinases (FGFRs 1-4) and four intracellular proteins (intracellular FGFs or iFGFs) that primarily function to regulate the activity of voltagegated sodium channels and other molecules. The canonical FGFs, endocrine FGFs, and iFGFs have been reviewed extensively by us and others. In this review, we briefly summarize past reviews and then focus on new developments in the FGF field since our last review in 2015. Some of the highlights in the past 6 years include the use of optogenetic tools, viral vectors, and inducible transgenes to experimentally modulate FGF signaling, the clinical use of small molecule FGFR inhibitors, an expanded understanding of endocrine FGF signaling, functions for FGF signaling in stem cell pluripotency and differentiation, roles for FGF signaling in tissue homeostasis and regeneration, a continuing elaboration of mechanisms of FGF signaling in development, and an expanding appreciation of roles for FGF signaling in neuropsychiatric diseases.

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Section: Development Of Fgf Pathway Inhibitors As Pharmaceuticalsmentioning

confidence: 99%

New developments in the biology of fibroblast growth factors

Ornitz

Itoh

2022

WIREs Mechanisms of Disease

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“…Finally, recognizing the importance of FGF5 overexpression in oncogenic processing, RNA aptamers that inhibit FGF5 expression have been proposed as a potential therapy for cancers dependent on FGF5 cell proliferation. 43 The protein structure modeling results do not provide an indisputable mechanism for pathogenicity of the W81C mutation reported here; the overall and local structural changes observed are modest at best. Nonetheless, the prediction of a second binding site for SO 4 in the mutant, albeit with a smaller multiplicity, may be an indication that the mutant's ability to bind to SO 4 -containing compounds, like heparan sulfate, may be different.…”

Section: S X 60smentioning

confidence: 57%

“…Zhou 41 reported that downregulation of FGF5 inhibits cell growth and invasion of human nonsmall cell lung cancer cells, and Zhao 42 has documented that increase of FGF5 expression correlates with poor survival in lung adenocarcinoma. Finally, recognizing the importance of FGF5 overexpression in oncogenic processing, RNA aptamers that inhibit FGF5 expression have been proposed as a potential therapy for cancers dependent on FGF5 cell proliferation 43 …”

Section: Discussionmentioning

confidence: 99%

A rare FGF5 candidate variant (rs112475347) for predisposition to nonsquamous, nonsmall‐cell lung cancer

Cannon‐Albright

Teerlink

Stevens

et al. 2023

Intl Journal of Cancer

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A unique approach with rare resources was used to identify candidate variants predisposing to familial nonsquamous nonsmall‐cell lung cancers (NSNSCLC). We analyzed sequence data from NSNSCLC‐affected cousin pairs belonging to high‐risk lung cancer pedigrees identified in a genealogy of Utah linked to statewide cancer records to identify rare, shared candidate predisposition variants. Variants were tested for association with lung cancer risk in UK Biobank. Evidence for linkage with lung cancer was also reviewed in families from the Genetic Epidemiology of Lung Cancer Consortium. Protein prediction modeling compared the mutation with reference. We sequenced NSNSCLC‐affected cousin pairs from eight high‐risk lung cancer pedigrees and identified 66 rare candidate variants shared in the cousin pairs. One variant in the FGF5 gene also showed significant association with lung cancer in UKBiobank. This variant was observed in 3/163 additional sampled Utah lung cancer cases, 2 of whom were related in another independent pedigree. Modeling of the predicted protein predicted a second binding site for SO4 that may indicate binding differences. This unique study identified multiple candidate predisposition variants for NSNSCLC, including a rare variant in FGF5 that was significantly associated with lung cancer risk and that segregated with lung cancer in the two pedigrees in which it was observed. FGF5 is an oncogenic factor in several human cancers, and the mutation found here (W81C) changes the binding ability of heparan sulfate to FGF5, which might lead to its deregulation. These results support FGF5 as a potential NSNSCLC predisposition gene and present additional candidate predisposition variants.

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“…Aptamers are single-stranded oligonucleotides that have a specific three-dimensional structure that allows them to bind to specific target molecules with high affinities. Aptamers have the potential to replace monoclonal antibodies because they present less immunogenicity and have an easier and a more cost-effective manufacturing process [16,17].…”

Section: Rna Therapeutics For Cancer Treatmentmentioning

confidence: 99%

Polymeric Carriers for Delivery of RNA Cancer Therapeutics

Mirón-Barroso

Correia

Frampton

et al. 2022

ncRNA

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As research uncovers the underpinnings of cancer biology, new targeted therapies have been developed. Many of these therapies are small molecules, such as kinase inhibitors, that target specific proteins; however, only 1% of the genome encodes for proteins and only a subset of these proteins has ‘druggable’ active binding sites. In recent decades, RNA therapeutics have gained popularity due to their ability to affect targets that small molecules cannot. Additionally, they can be manufactured more rapidly and cost-effectively than small molecules or recombinant proteins. RNA therapeutics can be synthesised chemically and altered quickly, which can enable a more personalised approach to cancer treatment. Even though a wide range of RNA therapeutics are being developed for various indications in the oncology setting, none has reached the clinic to date. One of the main reasons for this is attributed to the lack of safe and effective delivery systems for this type of therapeutic. This review focuses on current strategies to overcome these challenges and enable the clinical utility of these novel therapeutic agents in the cancer clinic.

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Specific inhibition of FGF5-induced cell proliferation by RNA aptamers

Cited by 16 publications

References 39 publications

New developments in the biology of fibroblast growth factors

New developments in the biology of fibroblast growth factors

A rare FGF5 candidate variant (rs112475347) for predisposition to nonsquamous, nonsmall‐cell lung cancer

Polymeric Carriers for Delivery of RNA Cancer Therapeutics

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