Noncoding RNAs and pancreatic cancer

Table 1 Main classes and function of human noncoding RNAs

RNA types	Length (nt)	Function
Small non-coding RNAs (< 200 nt)
Protein synthesis RNAs
Transfer RNAs	About 80	Carrying amino acids to connect with mRNA
Ribosomal 5S and 5.8S RNAs	121-200	Component of ribosomes
Small nucleolar RNAs	70-200	Involved in maturation of other non-coding RNAs
Small nuclear RNAs	About 150	Joining with proteins to form spliceosomes controlling alternative splicing
Regulatory RNAs
MicroRNAs	20-23	Negatively regulating gene expression by joining an enzyme and blocking mRNA, or speeding its breakdown
Small interfering RNAs	21-22	Silencing specific genes in a sequence-specific manner.
PIWI-interacting RNAs	About 25-33	Controlling retrotransposition and regulating methylation.
Promoter-associated short RNAs	< 200	Regulating gene expression through interaction with gene promoter sites
Long non-coding RNAs (> 200 nt)
Ribosomal 28S and 18S RNAs	200-5070	Component of ribosomes
Long intergenic non-coding RNAs or long intronic non-coding RNAs	> 200	Various
Telomere-associated ncRNAs	100 bp > 9 kb	Negative regulators of telomere
Antisense RNAs		Binding and blocking the translation of mRNA target
Promoter-associated short RNAs	> 200	Regulating gene expression through interaction with gene promoter sites
Transcribed-ultraconserved regions	200-799	Long-range enhancer-like activity, maintenance of splicing factor expression levels and transcription regulation

Table 2 Long noncoding RNAs dysregulated in pancreatic cancer

Names of lncRNAs	Genomic location	Expression	Roles in pancreatic cancer	Ref.
H19	11p15.5	Upregulated	Cell proliferation, migration, invasion, target therapy	[42-47]
HOTAIR	12q12.13	Upregulated	Cell proliferation, cell cycle, apoptosis, migration, invasion	[48-52]
HOTTIP	7p15.2	Upregulated	Cell proliferation, cell cycle, migration, invasion, drug resistance	[58,59]
MALAT-1	11q13	Upregulated	Cell proliferation, migration, invasion	[60-65]
PVT1	8q24.21	Upregulated	Drug resistance	[66-69]
HULC	6p24.3	Upregulated	Cell proliferation	[70]
AF339813	13q31.3	Upregulated	Cell proliferation, apoptosis	[71]
Gas5	1q25.1	Downregulated	Cell proliferation, cell cycle	[72]
ENST00000480739	12q13	Downregulated	Not mentioned	[73]

Table 3 Selected microRNAs in pancreatic cancer

MiRNA	Expression	Role	Target genes	Biological significance	Clinical significance
miR-21	Up	O	PTEN, EGFR, HER2/neu, PDCD4, Bcl2, TIMP2, TIMP3	Proliferation and cell division	Gem chemosensitivity, Biomarker, Prognosis, Potential target for treatment
miR-221/222	Up	O	CDKN1B, PUMA, PTEN, Bim	Cell cycle progression	Gem chemosensitivity, Biomarker for diagnosis, Prognosis, potential target for treatment
miR-192	Up	O	SIP1, cell cycle regulatory genes	Cell proliferation and migration, reduced apoptosis and cell cycle progression	Biomarker for diagnosis (serum)
miR-424-5p	Up	O	SOCS6	Cell proliferation and migration	Prognosis
miR-208	Up	O	CDH1	EMT	N
miR-155	Up	O	TP53INP1	Apoptosis	Biomarker for diagnosis, Prognosis
miR-10a/b	Up	O	HOXB8, HOXA1	Invasivity and metastasis	Gem chemosensitivity, Prognosis
miR-196a-2/196	Up	O	HOXB8, ANXA1, HMGA2	N	Biomarker for diagnosis, Prognosis
miR-375	Up	O	PDK1, 14-3-3zeta	Cell proliferation and apoptosis	Biomarker for diagnosis, Potential target for treatment
miR-210	Up	O	HOXA1, FGFRL1, HOXA9, COX10, E2F3, RAD52, ACVR1B, MNT	Regulating the interaction between pancreatic cancer cells and stellate cells	Biomarker for diagnosis, Prognosis
miR-301a	Up	O	Bim, NKRF	Proliferation and metastasis	Prognosis
miR-421	Up	O	DPANCREATIC CANCER4/Smad	Cell proliferation and colony formation	Potential target for treatment
miR-15/16	Up	O	Anti-apoptotic genes: bcl2l1, naip5, fgfr2 and mybl2	Apoptosis and tumor angiogenesis	Potential target for treatment
miR-124	Down	TS	RAC1	Cell proliferation, invasion and metastasis	N
miR-203	Down	TS	BIRC5, CAV1	Cell cycle progression, apoptosis, EMT	Indicator of the metastatic potential, potential target for treatment
miR-143	Down	TS	GET1, GET2, KRAS	Cell proliferation, invasion and metastasis	N
miR126,let-7	Down	TS	E2F2, c-Myc, KRAS, MAPK, STAT3	Cell proliferation	Chemosensitivity, potential target for treatment
miR-34a/b	Down	TS	TP53, Bcl-2	Apoptosis, DNA repair, cell cycle progression and angiogenesis	Prognosis, Chemosensitivity
miR-200 family	Down	TS	EP300, ZEB1, SIPI1	EMT	Prognosis, Chemosensitivity
miR-146a	Down	TS	IRAK-1, EGFR	Invasivity	Potential target for treatment
miR-96	Down	TS	KRAS, AKT	Tumor growth and invasion	Potential target for treatment

Up: Upregulated; Down: Downregulated; O: Oncogeneic; TS: Tumor suppressive; N: Not mentioned.