LncRNAs: Novel Biomarkers for Pancreatic Cancer
Abstract
:1. Introduction
2. Oncogenic LncRNAs in Pancreatic Cancer
3. Tumor Suppressor LncRNAs in Pancreatic Cancer
4. Diagnostic Role of LncRNAs in Pancreatic Cancer
5. Prognostic Role of LncRNAs in Pancreatic Cancer
6. Discussion
Author Contributions
Funding
Conflicts of Interest
References
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LncRNA | Sample | Cell Line | Interaction | Signaling Pathway | Clinical Properties | Method | Function | Ref. |
---|---|---|---|---|---|---|---|---|
C9orf139 | 54 pairs of tumor and ANTs | AsPC-1, BxPC3, PANC1, PaCa-2, SW-1990, HPDE6-C7 | miR-663a/Sox12 | _ | Tumor stage, lymph nodemetastasis | qRT-PCR, Western blotting, RNA immunoprecipitation, RNA pull-down, luciferase reporter assay | High expression of LncRNA C9orf139 is associated with the poor clinicopathological feature of PC patients | [9] |
CRNDE | 58 pairs of tumor and ANTs | SW-1990, PANC-1,CAPAN-1, JF305 BxPC-3,HPDE6-C7 | miR-384 | _ | Tumordifferentiation, tumor size, TNM stage, and lymph nodal metastasis | qRT-PCR, luciferase reporter assays, Western blotting, immunohistochemistry (IHC) analysis | LncRNA CRNDE plays an oncogenic role in PC tissue and cell lines via directly targeting miR-384 | [10] |
H19 | 139 invasive ductal carcinoma samples | PANC-1 | - | - | In situ hybridization, DNA microarray analysis, qRT-PCR | H19 affects cell motility but not cell growth rate | [11] | |
HOTAIR | _ | HPDE6-C7, SU.86.86, CFPPAC-1, SW-1990, PL45 | miR-34a | JAK2/STAT3 Pathway | _ | qRT-PCR, Western blotting, RNA pull-down | LncRNA HOTAIR can activate the JAK2/STAT3 pathway by targeting miR-34 and then enhancing the proliferation and invasion of PC cells | [12] |
HOTTIP | Panc-1, L3.6pL, and MiaPaCa2 | HOXA10, HOXB2, HOXA11, HOXA9, and HOXA1 | - | - | Illumina Human V.3 HT12 Beadchip array | HOTTIP regulates the proliferation, apoptosis, and migration of PC cells | [13] | |
HOXA-AS2 | 16 pairs of tumor and ANTs, 12 pairs of tumor and ANTs | AsPC-1, BxPC-3, PANC-1 | enhancer of zeste homolog 2 (EZH2), lysine-specific demethylase 1 (LSD1) | _ | _ | qRT-PCR | lncRNA HOXA-AS2 plays an oncogenic role in pancreatic cancer tissue | [14] |
LINC00976 | _ | CFPAC-1, MIA-PaCa-2, PANC-1, BxPC-3,CFPAC-1, ASPC-1, Panc03.27, Capan-2 | miR-137/ OTUD7B | EGFR/MAPK signaling pathway | Tumor size, lymph node metastasis, perineural invasion, vascularinvasion, distant metastasis ability | In situ hybridization (ISH), qRT-PCR | LINC00976 plays an oncogenic role in pancreatic cancer tissue and promotes invasion, migration, and proliferation via up-regulating OTUD7B and then targeting miR-137 | [7] |
LINC00462 | _ | SW-1990, BxPC3,PANC-1, AsPC-1, CFPAC-1, HPDE6-C7 | miR-665, TGFBR1, TGFBR2 | SMAD2/3 signaling pathway | Large tumor size, poor tumor differentiation, TNM stage, distant metastasis | qRT-PCR, CCK-8 assay, Western blotting, flow cytometry analyses, immunofluorescence | Over-expression of LINC00462 significantly promotes EMT and cell proliferation and suppresses cell apoptosis via up-regulating TGFBR1 and TGFBR2 | [8] |
LINC01559 | 55 pairs of tumor and ANTs | AsPC-1, BxPC-3, PANC-1, MIA- PaCa-2, SW-1990, HPDE | miR-1343-3p/RAF1 | ERK signaling pathway | Large tumors, lymph node metastasis, | RT-qPCR, RIP assay, CCK-8 assay, Western blotting, immunohistochemistry (IHC) | High expression of LINC01559 enhances proliferation of pancreatic cancer cells and metastasis by up-regulating Raf1 and activating the ERK pathway | [15] |
LINC00152 | 28 pairs of tumor and ANTs | BxPC3, Panc1, AsPC1, SW-1990, HPDE6-C7 | miR-150 | _ | _ | qRT-PCR, CCK-8 assay, EDU assay, luciferase reporter assay | LINC00152 can suppress miR-150 and then promote pancreatic cancer cells progressions | [16] |
LINC00958 | _ | PANC-1, Capan-2, SW-1990, BxPC-3,HPDE | miR-330-5p | _ | _ | qRT-PCR, Western blotting, fluorescent in situ hybridization (FISH), RNA immunoprecipitation (RIP) | LINC00958 enhances the EMT process and metastatic ability of PC cells | [17] |
LUCAT1 | 60 pairs of tumor and ANTs | BxPC-3, Capan2, AsPC-1, PANC-1, HPDE6c7 | miR-539 | _ | tumor size, lymphatic invasion. | qRT-PCR, in situ hybridization, Western blotting | LUCAT1 can enhance the invasion ability of cells by targeting miR-539 | [18] |
LINC00994 | 10 pairs of tumor and ANTs | PANC-1, AsPC-1, SW-1990 | miR-765-3p/RUNX2 | _ | _ | Microarrays, qRT-PCR, flow cytometry, luciferase assay, Western blotting | LINC00994 acts as an oncogene and its inhibition can suppress RUNX2 by targeting miR-765-3p | [19] |
LINC01207 | 36 pairs of tumor and ANTs | PANC-1, BxPC-3, Mpanc-96, PaTu-8988 | miR-143-5p | _ | _ | qRT-PCR, RNA pull-down, RNA immunoprecipitation (RIP), flow cytometry, immunofluorescence staining, Western blotting | Its inhibition can induce apoptosis and autophagy activity of PC cells via targeting miR-143-5p | [20] |
MACC1-AS1 | 98 pairs of tumor and ANTs, 124 pairs of tumor and ANTs | BxPC-3, PANC-1, MIA-PaCa-2, KP-2, AsPC-1, Capan-1 | PAX8 | NOTCH1 signaling pathway | _ | lncRNA microarray, qRT-PCR, luciferase analyses, RNAimmunoprecipitation | High expression of LncRNA MACC1-AS1 can induce pancreatic cancer cells proliferation and promote metastasis through regulating the PAX8/NOTCH1 signaling pathway | [6] |
OIP5-AS1 | 110 pairs of tumor and ANTs | PANC-1, BxPC-3, AsPC-1, CFPAC-1, HPDE6-C7 | miR-429, FOXD1, ERK pathway | ERK pathway | Tumor size, distant metastasis, TNM stage | qRT-PCR, RNA immunoprecipitation, RNA pull-down, luciferase reporter assay, Western blotting | High expression of LncRNA OIP5-AS1 can increase EMT process, invasion, and PC cell proliferation via activating the ERK pathway | [21] |
PVT1 | 30 pairs of tumor and ANTs | HPAC, DANG, BxPC-3, PANC1, ASPC-1, H6C7 | miR-519d-3p | glycolysispathway | lymph node metastasis | qRT-PCR, Western blotting, RNA immunoprecipitation (RIP) assay, RNA pull-down assay, immunohistochemistry (IHC) | PTV1 induces downregulation of miR-519d-3p and then promotes the progression of pancreatic cancer | [22] |
RP11-567G11.1 | 78 tumor tissues and 7 non-tumor tissues | SW-1990, BxPC-3, PANC-1 | _ | NOTCH signaling pathway | _ | In situ hybridization, CCK8 and flow cytometry, Western blotting, qPCR | Inhibition of LncRNA RP11-567G11.1 can induce apoptosis and suppress cancer cell proliferation | [23] |
SBF2-AS1 | _ | PANC-1, BxPC-3, SW-1990, Capan2, THP-1 | miR-122-5p | SMAD signaling pathway | _ | Flow cytometry, RNA-fluorescence in situ hybridization(FISH), qRT-PCR, Western blotting, RNA immunoprecipitation, RNA pull-down assays | The expression level of SBF2-AS1 is increased in M2 macrophage exosomes and plays an oncogenic role in pancreatic cancer tissue | [24] |
SNHG7 | 50 pairs of tumor and ANTs | PANC-1, SW-1990, BxPC-3 AsPC-1, HPDE | miR-146b-5, roundabout homolog 1(Robo1) | _ | Tumor size, distant metastasis, lymph node metastasis, | qRT-PCR, Flow cytometry analysis, luciferase reporter assay, RNA immunoprecipitation (RIP) assay, RNA pull-down assay, Western blotting | High expression of LncRNA SNHG7 can promote the progression of PC by positively affecting Robo1 | [25] |
SNHG12 | 15 pairs of tumor and ANTs | HPDE6, BxPC-3, CAPAN1, PANC1, SW-1990 | miR-320b | _ | _ | qRT-PCR, flow cytometry, luciferase assay | LncRNA SNHG12 can increase the invasion, EMT, and proliferation of cancer cells by negatively affecting miR-320b | [26] |
SNHG14 | 45 pairs of tumor and ANTs | CFPAC-1, BxPC-3, L3.6pl Panc-1, HPDE6C7 | miR-613 | _ | Poor tumor differentiation, advanced TNM stage, nodal metastasis | qRT-PCR, fluorescent in situ hybridization, flow cytometry, Western blotting | Increased expression of SNHG14 can promote the progression of pancreatic cancer by inhibiting caspase-3 activity and down-regulation of miR-613 | [27] |
SNHG15 | 48 pairs of tumor and ANTs | AsPC-1, BxPC-3, HPDE6 | zeste homolog 2 | _ | tumor size, TNM stage,lymph node, metastasis | qRT-PCR, Flow cytometry, Western blotting, RNA immunoprecipitation, chromatin immunoprecipitation (ChIP) | SNHG15 plays an oncogenic role in pancreatic cancer tissue by inversely regulating target genes | [28] |
SPRY4-IT1 | _ | BxPC-3, PANC-1 | Cdc20 | _ | _ | qRT-PCR, Western blotting, wound healing assay, Transwell assay | SPRY4-IT1 acts as an oncogene in PC tissue, and its inhibition induces depletion of PC progression | [29] |
TP73-AS1 | 77 pairs of tumor and ANTs | HPDE6-C7, SW-1990, CAPAN-1, JF305, PANC-1, BxPC-3 | miR-141 | _ | TNM stage, lymph node metastasis | qRT-PCR, luciferase reporter assays, Western blotting | High expression of lncRNA TP73-AS1 induces migration, invasion, and PC cell proliferation | [30] |
UCA1 | 120 pairs of tumor and ANTs | PANC-1, BxPC-3, Capan-1, SW-1990, HPDE6C-7 | _ | _ | Tumor size, depth of invasion, CA19-9 level, tumor stage | qRT-PCR, flow cytometry, Western blotting, | Low expression of LncRNA UCA1 can reduce the proliferation of PC cells and induce cell cycle arrest | [31] |
UCA1 | 36 pairs of tumor and ANTs | HPC-Y5, PANC-1, SW-1990, AsPC-1 | miR-96/FOXO3 | _ | _ | qRT-PCR, Western blotting, immunohistochemistry, flow cytometry, luciferase assay, RNA in situ hybridization | LncRNA UCA1 acts as an oncogene in PC tissue and cell lines via negative regulating miR-96 | [32] |
XIST | 30 pairs of tumor and ANTs | PANC-1, HEK293T | miR-141-3p, TGF-β2 | TGF-β signaling pathway | _ | qRT-PCR, luciferase reporter assay, Western blotting | LncRNA XIST plays an oncogenic role in PC tissue through targeting miR-141-3p and the TGF-β signaling pathway | [33] |
XIST | 64 pairs of tumor and ANTs | H6c7, Patu8988,SW-1990, BxPC-3, AsPC-1, CFPAC-1, PANC-1 | miR-133a/EGFR | EGFR/Akt signaling | Larger tumor size, perineuralinvasion, lymph node metastasis, shorter overall survival | qRT-PCR, BrdU cell proliferation assay, luciferase reporter assay | LncRNA XIST can induce PC cell proliferation through negatively regulating miR133a and positively regulating EGFR | [34] |
ZEB2-AS1 | 39 pairs of tumor and ANTs | AsPC-1, HPAC, Cfpac-1, PANC-1, HPDE | miR-204/ HMGB1 | _ | _ | q-RT-PCR, Western blotting immunofluorescence assay, luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay, LncRNA array | Overexpression of LncRNA ZEB2-AS1 induces cell proliferation and invasion by negatively affecting miR-204 | [35] |
LncRNA | Sample | Cell Line | Interaction | Signaling Pathway | Clinical Properties | Method | Function | Ref. |
---|---|---|---|---|---|---|---|---|
ENST00000480739 | 35 patients with pancreatic cancer | ASPC-1, BXPC-3, CFPAC-1, PANC-1 and SW1990 | OS-9 | - | Tumor node metastasis stage and lymph node metastasis | Transwell invasion assay, ELISA, Western blot | ENST00000480739 participates in tumor metastasis and progression | [43] |
LINC01111 | _ | HPDE, PANC-1, MIA-PaCa-2,SW-1990, Capan-2, Panc 03.27, BxPC-3, CFPAC-1 | miR-3924 | SAPK/JNK signaling pathway | TNM stage (negatively), survival (positively) | qRT-PCR, EdU incorporation assay, scratch wound healing assays, Western blotting, RNA microarrays, in situ hybridization | LINC01111 plays a tumor-suppressive role in PC tissue and cell lines via inhibition of the SAPK/JNK signaling pathway | [38] |
LINC01963 | 67 pairs of tumor and ANTs | PANC-1, CFPAC-1, BxPC-3, SW-1990, AsPC1, HPDE6-C7 | miR-641/TMEFF2 | _ | Distantmetastasis, TNM stag | qRT-PCR, flow cytometry assay, luciferase assay, RNA immunoprecipitation, Western blotting | High expression of LncRNA LINC01963 can induce inhibition of pancreatic cancer progression via negatively regulating miR-641 | [39] |
DGCR5 | 20 pairs of tumor and ANTs | SW-1990, PANC-1, HPDE6-C7 | miR-27a-3p/BNIP3 | p38 MAPK pathway | _ | qRT-PCR, Western blotting, RNA immunoprecipitation (RIP), RNA pull-down assay, luciferase reporter assay, flow cytometric (FCM) analysis | Down-regulation of lncRNA DGCR 5 affects apoptosis through regulating BNIP3 and the p38 MAPK pathway | [42] |
MEG3 | 30 pairs of tumor and ANTs | PANC-1 | PI3K protein | PI3K/AKT/Bcl-2/Bax/cyclin D1/P53 and PI3K/AKT/MMP-2/MMP-9 signaling pathways | Tumor size, metastasis, and vascular invasion | Immunohistochemistry (IHC) assay, qRT-PCR, Western blotting | LncRNA MEG 3 acts as a tumor-suppressor in PC tissue and cell lines | [40] |
GAS5 | 22 pairs of tumor and ANTs | PANC-1, BxPC-3, HPDE6-C7 | miR-32-5p | PTEN signaling pathway | _ | qRT-PCR, Western blotting, flow cytometry analysis, RNA immunoprecipitation (RIP) assay, RNA pull-down assay | GAS5 exhibits tumor suppressor activity in PDAC tissue samples | [41] |
LINC00261 | _ | CFPAC-1, BxPC-3, PANC-1, AsPC-1, HPDE6-C7 | miR-23a-3p | _ | _ | qRT-PCR, flow cytometry, Western blot | A low expression level of LINC00261 can promote PC progression by targeting miR-23a-3p | [44] |
LncRNA | Expression Pattern | Detection Method for LncRNAs | Sample | Area Under the Curve (AUC) | References |
---|---|---|---|---|---|
LncRNA-UFC1 | Up-regulation | qRT-PCR | 48 serum samples of patients | 0.810 | [47] |
RP11-263F15.1 | Up-regulation | Microarray, qRT-PCR | 71 pairs of tumor and ANTs | 0.843 | [48] |
ABHD11-AS1 | Up-regulation | qRT-PCR | 15 serum samples of patients and 30 healthy individuals | 0.887 | [49] |
LINC00675 | Up-regulation | Microarray, qRT-PCR | 45 pairs of tumor and ANTs | 0.928 | [45] |
HULC | Up-regulation | qRT-PCR | 60 serum samples of patients and 60 healthy individuals | 0.856 | [50] |
C9orf139 | Up-regulation | qRT-PCR | 54 pairs of tumor and ANTs | 0.923 | [46] |
PVT1 | Up-regulation | qRT-PCR | Salivary samples from 55 patients with resectable pancreatic cancer, 20 patients with benign pancreatic lesions, and 55 normal controls | 0.84 (cancer vs. benign lesion), 0.90 (cancer vs. healthy state) | [51] |
HOTAIR | Up-regulation | qRT-PCR | 0.86 (cancer vs. benign lesion), 0.88 (cancer vs. healthy state) |
LncRNA | Expression Pattern | Sample | Kaplan–Meier Analysis | Multivariate Analysis | References |
---|---|---|---|---|---|
RUNX1-IT1 | Up-regulated | 83 tumor tissues and 38 ANTs and 15 normal pancreatic tissues | Overexpression of lncRNA RUNX1-IT1 was associated with poor overall survival | Expression of lncRNA RUNX1-IT1 was identified as an independent prognostic factor for pancreatic cancer patients | [52] |
ENSG00000254041.1 | Up-regulated | 70 pairs of tumor and ANTs | Its high expression was associated with poor overall survival | Expression of lncRNA ENSG00000254041.1 can be an independent predictor of pancreatic cancer survival | [53] |
MALAT1 | Up-regulated | 45 pairs of tumor and ANTs | Its high expression was associated with poor disease-free survival | Expression of lncRNA MALAT1 can be an independent prognostic factor for disease-specific survival in patients | [54] |
LOC285194 | Down-regulated | 85 pairs of tumor and ANTs | Low expression of lncRNA LOC285194 was associated with poor overall survival | Low expression of lncRNA LOC285194 can be an independent poorprognostic factor in pancreatic cancer patients | [55] |
LncRNA-UFC1 | Up-regulated | 48 serum samples of patients | Overexpression of lncRNA-UFC1 was associated with shorter progression-free survival and overall survival | Expression levels of lncRNA-UFC1 were identified as independent prognostic factors in patients | [47] |
RP11-263F15.1 | Up-regulated | 71 pairs of tumor and ANTs | Increased lncRNA RP11-263F15.1 expression level was associated with poor overall survival | The expression level of lncRNA RP11-263F15.1 was not independent of prognostic factors in patients | [48] |
BC008363 | Down-regulated | 30 pairs of tumor and ANTs | Overexpression of lncRNA BC008363 indicated better overall survival | _ | [56] |
MEG3 | Down-regulated | 25 pairs of tumor and ANTs | Increased LncRNA MEG3 expression was associated with longer overall survival | _ | [57] |
HULC | Up-regulated | 25 pairs of tumor and ANTs | A high expression level of LncRNA HULC was associated with shorter overall survival | The expression level of LncRNA HULC identified as an independentpredictor for overall survival | [58] |
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Ghafouri-Fard, S.; Fathi, M.; Zhai, T.; Taheri, M.; Dong, P. LncRNAs: Novel Biomarkers for Pancreatic Cancer. Biomolecules 2021, 11, 1665. https://doi.org/10.3390/biom11111665
Ghafouri-Fard S, Fathi M, Zhai T, Taheri M, Dong P. LncRNAs: Novel Biomarkers for Pancreatic Cancer. Biomolecules. 2021; 11(11):1665. https://doi.org/10.3390/biom11111665
Chicago/Turabian StyleGhafouri-Fard, Soudeh, Mohadeseh Fathi, Tianyue Zhai, Mohammad Taheri, and Peixin Dong. 2021. "LncRNAs: Novel Biomarkers for Pancreatic Cancer" Biomolecules 11, no. 11: 1665. https://doi.org/10.3390/biom11111665