Non-coding landscapes of colorectal cancer

Table 1 Functions of microRNAs deregulated in colorectal cancer

microRNA	Oncogene/tumor suppressor	Process in CRC	Targets	PMID
Let-7	Tumor suppressor	Cell proliferation, migration, invasion, metastasis	KRAS, MMP11, PBX3	23167843, 21984339, 16651716
miR-1	Tumor suppressor	Cell proliferation, invasion, migration	MET	22179665
miR-16	Tumor suppressor	Cell proliferation	PTGS2	22049153
miR-17-92 cluster	Oncogene	Angiogenesis, proliferation, metastasis	TSP-1, CTGF, PTEN, BCL2L11, E2F1, E2F2, E2F3, TGFBR2, CDKN1A, BIM	19460962, 16878133, 22308110, 24212931, 21883694
miR-18a	Tumor suppressor	Cell proliferation, migration	CDC42, HNRNPA1	25379703, 24166503
miR-21	Oncogene	Cell proliferation, migration, invasion, metastasis, stemness	PDCD4, CCL20, Cdc25A, TGFBR2, PTEN, RHOB, RASA1	22677902, 17968323, 22099878, 19826040, 22120473, 23788041, 23544170, 23174819, 22072622, 21872591, 25663768
miR-23b	Tumor suppressor	Cell migration, invasion, angiogenesis	FZD7, MEKK1, PAK2, TGFBR2, RRAS2, PLAU, VEGF	22109528
miR-31	Oncogene	Cell proliferation, invasion, migration	CDKN2B, RASA1	21062447, 25202407, 23322774
miR-34	Tumor suppressor	Migration, invasion, metastasis, EMT	IL6R, ZNF281, MET, SNAIL, CTNNB1, SLUG, ZEB1	24642471, 24185900, 23243217, 22134354
miR-101	Tumor suppressor	Cell proliferation, motility, invasion	EP4, PTGS2	22353936, 19133256
miR-103/miR-107	Oncogene	Invasion, migration, metastasis	DAPK, KLF4	22593189
miR-106a	Oncogene	Cell proliferation, migration, invasion, metastasis	RB1, TGFBR2	23178825, 22912877
miR-126	Tumor suppressor	Cell proliferation, migration, invasion, metastasis, angiogenesis	PIK3R2, IRS1, CXCR4, VEGF	18663744, 24312276, 24189753, 24653631, 23900443
miR-135a	Oncogene	Cell proliferation, migration, invasion	MTSS1	23017832
miR-135b	Oncogene	Cell proliferation, invasion	APC, TGFBR2, DAPK1	18632633, 24735923
miR-143	Tumor suppressor	Cell proliferation, metastasis	KRAS, ERK5, MACC1, HK2, IGF1R, DNMT3A	19137007, 16969504, 22533346, 22691140, 23574723, 19638978
miR-145	Tumor suppressor	Cell proliferation, angiogenesis	MYC, CDK6, E2F1, CCND2, p70S6K1, PAK4	21278451, 15944709, 19843336, 21917858, 22766504
miR-148a	Tumor suppressor	Cell proliferation	BCL2	21455217
miR-155	Oncogene	Cell proliferation, migration, invasion, chemoresistance	CLDN1	23588589, 23036199
miR-181a	Oncogene	Cell proliferation, invasion, metastasis, EMT	PTEN, WIF1	24685694, 24755295
miR-200c	Tumor suppressor	Cell proliferation, invasion, migration, EMT, metastasis	ZEB1, ETS1, FLT1, CDH1, VIM	22735571, 22407310
miR-210	Oncogene	Cell migration, invasion	VMP1	24632577
miR-320a	Tumor suppressor	Cell proliferation, migration, invasion, metastasis, EMT	CTNNB1, RAC1, NRP1	22459450, 24265291, 22134529
miR-372	Oncogene	Cell proliferation	TXNIP, LATS2	22660396, 22456107
miR-638	Tumor suppressor	Cell invasion, migration	SOX2, TSPAN1	24885288, 25301729
miR-720	Oncogene	Cell proliferation, invasion, migration	STARD13	25286763, 22660396

For all miRNAs are reported: (1) their function in CRC (oncogene, or tumor suppressor); (2) the biological processes they are involved in; (3) their mRNA validated targets; (4) bibliographic references reported as PubMed ID (PMID).

Table 2 Functions of long non-coding RNAs deregulated in colorectal cancer

lncRNA	Oncogene/tumor suppressor	Biological process	Target	PMID
AK123657	Tumor suppressor	Cell proliferation, invasion		24809982
BANCR	Oncogene	Cell migration, EMT		25013510
BX648207	Tumor suppressor	Cell proliferation, invasion		24809982
BX649059	Tumor suppressor	Cell proliferation, invasion		24809982
CCAT1-L	Oncogene	MYC expression regulation	MYC-335	24662484
CCAT2	Oncogene	WNT signalling pathway activation	TCF7L2, MYC, miR-17-5p, miR-20a	23796952
CRNDE	Oncogene	Epigenetic remodelling of chromatin		19571010
H19	Oncogene	miR-675 precursor, cell proliferation, EMT, miRNA sponge	let-7	17237358, 19926638
HOTAIR	Oncogene	HOXD expression regulation, metastasis	HOXD10, PGR	24075995, 20393566
MALAT1	Oncogene	pre-mRNA metabolism, target gene expression regulator, tumor suppressor protein regulation, cell cycle progression, cell migration, MET	PSF, E2F1	17270048, 16878148, 18067128, 22078878, 22722759
mascRNA	Oncogene	Cell proliferation, invasion		21503572
N-BLR	Oncogene	Apoptosis, cell migration, invasion		http://dx.doi.org/10.1101/004796
PVT1	Oncogene	miRNAs precursor, cell proliferation, invasion		18194563, 25043044
TUSC7	Tumor suppressor	Cell proliferation, miRNA sponge	miR-211	23558749

For all lncRNAs are reported: (1) their function in CRC (oncogene, and tumor suppressor); (2) the biological processes they are involved in; (3) their validated targets; (4) bibliographic references reported as PubMed ID (PMID). LncRNA: Long non-coding RNA.

Table 3 Diagnostic and prognostic cellular microRNAs in colorectal cancer

Clinical feature	Oncogenes	Tumor suppressor genes	PMID
Fluorouracil based therapy positive response	let-7g, miR-181b, miR-26a-1 (SNP)		18172508, 20585341
Metastasis	miR-21, miR-372, miR-720, miR-181a, miR-135a, miR-335	miR-126, miR-34a, miR-27a (SNP)	22120473, 24653631, 22456107, 25286763, 23243217, 24755295, 25078482
Poor fluorouracil based therapeutic prognosis	miR-21		18230780
Progression		miR-100 (SNP)	20585341
Survival	miR-21, miR-17, miR-181a, miR-181b, miR-372, miR-720, miR-106a, miR-20a, miR-203, miR-423 (SNP), miR-196a-2 (SNP)	miR-200c, miR-320, miR-498, miR-608 (SNP), miR-219-1 (SNP)	18230780, 18079988, 22065543, 24098024, 18676867, 22456107, 25286763, 22028396, 22661538, 22161766
Tumour size	miR-720	miR-143, miR-145	18196926, 25286763
Undifferentiated phenotype	miR-21	miR-143, miR-145	18196926

Cancer-related phenotypes that may be predicted by expression analysis of oncomiRNAs and tumor suppressor miRNAs. miRNAs: MicroRNAs.

Table 4 Diagnostic and prognostic cellular long non-coding RNAs in colorectal cancer

Clinical feature	Oncogenes	Tumor suppressor genes	PMID
Disease-free survival	AK026784, AK024680, MALAT1	AK123657, CR622106, BX649059, BX648207, TUSC7, RPL34-AS1	24809982, 25031737, 23680400, 24908062
Distant metastasis	91H, PCAT1, CCAT1	TUSC7, RPL34-AS1	25058480, 23640607, 23594791, 23680400, 24908062
Liver metastasis	HOTAIR, HULC	ncRAN	21862635, 24519959, 19445043
Lymph node metastasis	PVT-1, AK021444, ENST00000425785, AK307796	ENST00000465846	24196785, 25009386
Metastasis risk	MALAT1		25031737
Overall survival	MALAT1, PVT-1, PCAT1	ncRAN, uc.73	25031737, 24196785, 24519959, 23640607, 22328099
Plasma diagnostic marker	CRNDE		22393467
Poor prognosis	HOTAIR, 91H, PVT-1		21862635, 25058480, 24196785
Tumour risk	PRNCR1 (SNP)		24330491
Tumour size	HOTAIR, PRNCR1 (SNP)	TUSC7	21862635, 23680400, 24330491
Tumour stage	CCAT1	lincRNA-p21, TUSC7, RPL34-AS1	24012455, 23594791, 23680400, 24908062
Undifferentiated phenotype	HOTAIR, PRNCR1 (SNP)	ncRAN	21862635, 24519959, 24330491
Venous invasion	PVT-1	lincRNA-p21	24196785, 24012455

Cancer-related phenotypes that may be predicted by expression analysis of oncogenic and tumor suppressive long non-coding RNAs.

Table 5 Diagnostic and prognostic circulating non-coding RNAs in colorectal cancer

Clinical feature	Oncogene ncRNAs	Tumor suppressor ncRNAs	PMID
Diagnostic	miR-17-3p, miR-92a, miR-29a, miR-18a, miR-19a, miR-19b, miR-15b, miR-335, miR-221, exo-let-7a, exo-miR-1229, exo-miR-1246, exo-miR-150, exo-miR-21, exo-miR-223, exo-miR-23a, miR-378, miR-21, CRNDE, miR-155, miR-200c, miR-210	miR-601, miR-760, miR-143	19201770, 19876917, 23267864, 22970209, 20880178, 24705249, 25547322, 22868372, 22393467, 24310813
Metastasis detection	miR-29a, miR-21		22018950, 23704278
Survival	miR-141, miR-221, miR-21		21445232, 20880178, 23704278
Tumour size	miR-21		23704278
Tumour stage	miR-141		21445232

Cancer-related phenotypes that may be predicted by expression analysis of plasma/serum circulating oncogenic and tumor suppressive non-coding RNAs (ncRNAs). Exo-miR: MiRNAs purified from exosomes.