Methods and compositions for modulating lncRNAs and methods of treatment based on lncRNA expression
Among the various aspects of the present disclosure is the provision of a methods and compositions for modulating lncRNAs and methods of treatment based on lncRNA expression.
1. A method of treating a subject having cancer expressing RAMS11, the method comprising:
providing a biological sample from the subject, the biological sample comprising long noncoding RNA associated with metastasis (RAMS);
measuring a level of RAMS11 (SEQ ID NO: 1) in the biological sample;
administering to the subject, when the measured level of RAMS11 is overexpressed compared to a control sample, a treatment comprising at least one antisense oligonucleotide (ASO) selected from CAACTTCCAGCAAGAT (SEQ ID NO: 41) and AGAACTGCTAAAAGTG (SEQ ID NO: 42); and
wherein the cancer expressing RAMS11 is selected from the group consisting of colorectal cancer (CRC), lung cancer, head or neck cancer, and kidney cancer.
2. The method of claim 1 , wherein the subject is not treated with a topoisomerase inhibitor.
3. The method of claim 1 , wherein the subject is further administered a therapeutically effective amount of: a kinase inhibitor, an alkylating agent, an antineoplastic antibiotic, or an anthracycline antibiotic.
4. The method of claim 1 , wherein the ASO reduces expression of one or more RAMS11 exons selected from the group consisting of:
(SEQ ID NO: 2)
AGAATGCCAAAGAGCAGCAGGATGGATCCAGCATCCTCTCCTGATAAAAG
AGGGCTAGAAGACGGGAGGCTCCGGGAAGTCTACTGG;
(SEQ ID NO: 3)
AGTCATGAAGACACTGAAAAGTGATGAATCCACATAACCATGACACTGGA
AATGAAGTTTGAGTGGCAGTCAGAATCTGGGAGGAAGCATTGCTAAGTGA
AAATCTTATGGAGCTTGACTAAAAATCCCTGTCAGGAACCGTCAAAAGCT
GTGTCCCTGACATGAAAAATCTTGCTGGAAGTTGAGAGAGGTTTATGCCT
ACTCCGTGATCCGGGAACACAAGACCTTTACCAACCAAAAAAGTGGATAG
CTGTTCTTCTGCTGTGAAGGTTAATAAAG;
(SEQ ID NO: 4)
AACGCCAGAAGTGCCAAGCAATTAACAACCCCAGAAGCAACCCTTAACCA
ATGATTAAATAAAGTGGATGATTACATACCCAAGCTCCTTCAACTCCCAG
GGACATAATTCTGAG;
(SEQ ID NO: 5)
GGATGGAAAACAAACTGAAACTGGCTCAAGTGAATGCTCACTGGAAGGCT
TACTGGAAAACTTACTGGAAGGATGTGAGGACATGTTCGGGAATCTATTT
GCAGAAAACATATTCAG;
and
(SEQ ID NO: 6)
CCCTGTCCACCACAGCCAGCTGGCTGAAGAGCTCAAAAGGCAAGAAATCA
GCAAGAGAGAGAGATGAAGCATGAGAAATGAGCAAAAAACACCCAGCACA
TCATAATCTTGGACAGTTTAGCAGTACATGAAAATAGATGGTCCTCGCCC
CAAGGGACTGCAGTAACCCTGAATAAACAGGATGTCTCTCACTTTTAGCA
GTTCTTTCTGTGCTAGTATTGGGGAAATATATTTTTGGCTGCATGCAAAA
TGGTAAAAGACATCTATTAAGAAAATGAAAACAATGCTTCTGTTTTAGAC
GAAGCTTTTGAAGGTTTAAGGATCACCTATTTATTGACAAAATTGTTTCC
GTGGCTTAAAA.
5. The method of claim 1 , wherein the biological sample comprises tumor cells, circulating tumor cells (CTCs), or formalin-fixed paraffin-embedded (FFPE) tissue, or frozen tissue.
6. The method of claim 1 , wherein the biological sample comprises tumor long noncoding RNAs (lncRNAs).
7. The method of claim 1 , wherein the biological sample is tumor tissue.
8. The method of claim 1 , wherein the biological sample is a biopsy sample.
9. The method of claim 1 , wherein the cancer is selected from the group consisting of: colorectal adenocarcinoma, lung adenocarcinoma, lung squamous cell carcinoma, head and neck squamous cell carcinoma (HNSC), and kidney renal papillary cell carcinoma (KIRP).
10. The method of claim 1 , wherein overexpressed RAMS11, indicates a bad outcome.
11. The method of claim 1 , wherein overexpressed RAMS11 indicates aggressive CRC.
12. The method of claim 1 , wherein overexpressed RAMS11 indicates a poor prognosis.
13. The method of claim 1 , wherein RAMS11 is detected by qPCR.