Compositions and methods to modulate tumor microenvironment associated long noncoding rnas

The modulator of any one of the preceding claims, wherein one or more enhancers are within a genomic locus encoding the lncRNA, wherein the one or more enhancers are associated with the CAF.

The modulator of any one of the preceding claims, wherein the expression or activity of the lncRNA is not upregulated in a cell that is not associated with cancer.

The modulator of any one of the preceding claims, wherein one or more protein-coding genes are at most 100, 200, 300, 400, or 500 nucleotides upstream or downstream of or within the genomic locus encoding the lncRNA, wherein the one or more protein-coding genes are associated with the CAF.

The modulator of any one of the preceding claims, wherein the lncRNA comprises any one of lncRNAs listed in Table 10 or Table 12, or a fragment thereof.

The modulator of any one of the preceding claims, wherein the lncRNA comprises XLOC 055514, XLOC_055515, XLOC_069921, XLOC 005184, ENSG00000203585, SHARED_00113753, ENSG00000288903, ENSG00000230838 (LINC01614), ENSG00000244137, or a fragment thereof, as listed in Table 10.

The modulator of any one of the preceding claims, wherein the modulator comprises an endonuclease complex guided by a nucleic acid, wherein the nucleic acid targets the lncRNA or a genomic locus thereof.

A modulator comprising an antisense oligonucleotide (ASO), wherein the ASO comprises at least 10, 11, 12, or 13 consecutive nucleotides with no more than 1, 2, or 3 mismatches from SEQ ID NO:

• 2, 4, 5, 9-11, 15, 16, 18, 19, 24-26, 34 or 38-40.

A method of diagnosing or monitoring a cancer in a subject, the method comprising:

• (a) obtaining a sample from the subject;
• (b) detecting an expression and/or an activity of a biomarker from the sample, wherein the biomarker comprises an lncRNA comprising a nucleic acid sequence listed in Table 11 or a fragment thereof, or transcribed from a genomic region or a subset thereof listed in Table 10 or Table 12;
• and (c) diagnosing or monitoring the cancer prognosis based on the expression and/or the activity of the biomarker.

A method of predicting severity and progression of a cancer in a subject, the method comprising:

• (a) obtaining a sample from the subject;
• (b) detecting an expression and/or an activity of a biomarker from the sample, wherein the biomarker comprises an lncRNA comprising a nucleic acid sequence listed in Table 11 or a fragment thereof, or transcribed from a genomic region or a subset thereof listed in Table 10 or Table 12;
• and (c) diagnosing the subject to have a more severe or a progression of the cancer if the expression and/or the activity of the biomarker is at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% higher when compared to a control.

A method of monitoring an efficacy or therapeutic resistance of a therapy treating a cancer in a subject, the method comprising:

• (a) obtaining a sample from the subject;
• (b) detecting an expression and/or an activity of a biomarker from the sample, wherein the biomarker comprises an lncRNA comprising a nucleic acid sequence listed in Table 11 or a fragment thereof, or transcribed from a genomic region or a subset thereof listed in Table 10 or Table 12;
• and (c) concluding the therapy treating the cancer is effective or is less likely to develop therapeutic resistance if the expression and/or the activity of the biomarker is at least 50%, at least 60%, at least 70%, at least 80%, at least 90% reduced by the therapy.