Dna damage dependent microrna signature for cancers, methods and uses related thereto
AssigneeNational Institute of Immunology
InventorSagar SENGUPTA
Life of this patent
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Abstract
The present invention related to microRNA (miR) signatures also called DNA damage sensitive miRs (DDSMs) which responds to the levels of DNA damage. The present invention provides method for identification of DDSMs which are upregulated by a common transcription factor (CDX2). Further, the present invention also provides miR inhibitors along with nanoparticle or hydrogel or adenoviral based delivery system for administering the same and kits comprising the same. The microRNA (miR) signature of the present invention can be used as biological markers to detect earliest stages of cancers particularly colon cancers. The present invention also provides a method of treatment of other types of cancer and related diseases.
Claims18
Deoxyribo-Nucleic Acid (DNA) damage sensitive microRNA signatures (DDSMs), comprising one or more sequences, wherein the one or more sequences comprise SEQ ID NO. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, and combinations thereof.
A method for identifying Deoxyribo-Nucleic Acid (DNA) damage sensitive microRNA signatures (DDSMs), which respond to level of DNA damage, wherein said method comprises the steps of:
- a. isolating RNA from two pair of isogenic cell lines, one with and one without BLM helicase;
- b. conducting small RNA sequencing with isolated RNA of step (a);
- c. observing expression levels of micro RNAs (miRNAs, miRs) in both the isogenic pairs in absence of BLM helicase expression;
- d. validating relative expression of upregulated miRs obtained from step (b) in the same isogenic pairs of cells;
- e. further validating the expression of upregulated miRs in isogenic lines of colon cancer origin;
- and
- f. identifying DDSMs having upregulated by common transcription factor CDX2.
A method of treatment of cancer, comprising administering to a colon cancer patient in need thereof miR inhibitors against Deoxyribo-Nucleic Acid (DNA) damage sensitive microRNA signatures (DDSMs) selected from SEQ ID NO. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16 into tumours of the colon cancer patient.
A kit for detecting Deoxyribo-Nucleic Acid (DNA) damage sensitive microRNA (miR) signatures (DDSMs) and levels of CDX2 expression, wherein said kit comprises a microfluidic system in which patient's body fluid or tissue is added, from which miR and mRNA are extracted, converted into complementary DNA (cDNA) by reverse transcription PCR (RT-PCR), and a level of the cDNA quantitatively determined.
Dependencies are inferred from the claim text.