Method for inhibiting the expression of cancer-promoting factors
Inventors
Asahara, Hiroshi • Chiba, Tomoki • Abe, Kentaro
Assignees
Nippon Zoki Pharmaceutical Co Ltd • Tokyo Medical and Dental University NUC
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Publication Number
US-12253515-B2
Publication Date
2025-03-18
Expiration Date
Abstract
Provided are an expression inhibitor of a cancer promoting factor based on the discovery of a new factor influencing the expression amount/level of a cancer promoting factor, and a development tool therefor. Provided are also a diagnostic agent and a diagnosis method for cancer. More specifically provided are: an expression inhibitor of a cancer promoting factor containing at least one kind of inhibitor selected from the group consisting of RBMS expression inhibitor and RBMS function inhibitor; a screening method using as an indicator the expression or the function of RBMS; an expression cassette useful for the method; as well as a diagnostic agent containing a product detection agent for RBMS gene expression and cancer detection method using as an indicator RBMS gene expression amount/level.
Core Innovation
The invention is directed to RBMS as a post-transcriptional regulator that increases expression of cancer promoting inflammatory cytokines and metastasis-related factors. RBMS2 is described as promoting increased expression through AU-rich elements in 3′UTRs, as part of an RBMS-driven paradigm of mRNA stabilization via AU-rich elements.
The problem addressed is cancer for which inhibition of expression of at least one cancer promoting factor is needed. The described approach targets RBMS2 expression in a patient having at least one type of cancer in need of inhibition of expression of cancer promoting factors.
The documented examples and supporting findings described in the partial content include that RBMS2/1/3 stabilize IL-6/IL-8 and metastasis-related factors, that RBMS knockdown reduces cancer growth, migration, infiltration, and metastasis, and that RBMS binds AU-rich elements, including a referenced F3 3′UTR. The partial content further states correlations with KRAS mutations and poor prognosis in highly malignant cancers.
Claims Coverage
The independent claim covers administering an RBMS2 expression inhibitor to a patient to inhibit expression of at least one cancer promoting factor. It is focused on four inventive forms of RBMS2 expression inhibition, and is supported by dependent claims that enumerate target cancer-promoting factors and narrow the cancer types and RAS mutation scope.
Administering an RBMS2 expression inhibitor to inhibit cancer promoting factor expression
A method for inhibiting the expression of at least one cancer promoting factor by administering to a patient having at least one type of cancer in need of inhibition of the expression of at least one cancer promoting factor an RBMS2 expression inhibitor.
RBMS2 expression inhibitor selection among siRNA, translation-inhibiting miRNA, antisense nucleic acid, or expression vectors
The RBMS2 expression inhibitor is selected from the group consisting of a RBMS2-specific siRNA, a miRNA inhibiting the translation of a gene encoding RBMS2, a RBMS2-specific antisense nucleic acid, and expression vectors thereof.
Targeting a selected set of cancer promoting factors
The cancer promoting factor is selected from the group consisting of CSF2, IL-6, ADAM10, ADM, CTGF, HBEGF, HILPDA, IL-24, THBS1, MYC, TGFB2, ITGA6, F3, PTP4A1, HSPA5, PLAU, CYR61, ITGA6, EDIL3, CSF1, ITGB1 and MMP1.
Treating specified cancer types including RAS-mutant and highly malignant cancer
The at least one type of cancer is selected from the group consisting of pancreatic cancer, colorectal cancer, lung cancer, bile duct cancer and breast cancer, or a cancer of a type of RAS gene mutation, and/or a highly malignant cancer.
Specializing RAS gene mutation to KRAS gene mutation
The RAS gene mutation is a KRAS gene mutation.
Overall, the claim set centers on inhibiting cancer promoting factor expression by administering an RBMS2 expression inhibitor, selected from RBMS2-specific siRNA, translation-inhibiting miRNA, RBMS2-specific antisense nucleic acid, or expression vectors. Dependent claims narrow the targeted cancer-promoting factors to an enumerated set and restrict applicable cancers to specific cancer types and RAS-mutant, including KRAS-mutant, and highly malignant cancers.
Stated Advantages
Inhibits the expression of at least one cancer promoting factor in a patient having at least one type of cancer in need of inhibition of the expression of at least one cancer promoting factor.
RBMS2/1/3 stabilize IL-6/IL-8 and metastasis-related factors, and RBMS knockdown reduces cancer growth, migration, infiltration, and metastasis.
RBMS binds AU-rich elements in 3′UTRs, including a referenced F3 3′UTR.
Correlates with KRAS mutations and poor prognosis in highly malignant cancers.
Documented Applications
Diagnostic and cancer detection/progression use in which RBMS gene expression level is used as an index for cancer detection and the degree of progression of cancer.
Cancer detection/progression in highly malignant cancers, including correlations of RBMS activity with KRAS mutations and poor prognosis.
Screening reagents and indices for finding inhibitors of RBMS expression/function, including reporter-based approaches, RBMS–RNA binding assays, and RBMS-overexpression cell assays.
Use of RBMS-targeting inhibitors as RBMS expression inhibitors and RBMS function inhibitors, including RBMS-specific siRNA/miRNA/antisense nucleic acids and vectors.
Therapeutic method of inhibiting RBMS2 expression by administering RBMS2 expression inhibitors to a patient with cancer needing inhibition of cancer-promoting factor expression.
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