Molecule Information

General Information of the Molecule (ID: Mol01274)

• Name: CDKN2B antisense RNA 1 (CDKN2B-AS1) ,Homo sapiens
• Synonyms: CDKN2B-AS1
• Molecule Type: LncRNA
• Gene Name: lncRNA-SRLR
• Gene ID: 100048912
• Location: chr9:21994139-22128103[+]
• Ensembl ID: ENSG00000240498
• HGNC ID: HGNC:34341

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

Approved Drug(s) 4 drug(s) in total

Paclitaxel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [1]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Resistant Drug: Paclitaxel
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung adenocarcinoma
• The Studied Tissue: Lung
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.86E-05; Fold-change: 7.84E-01; Z-score: 4.01E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Mitochondrial signaling pathway; Activation; hsa04217
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: A549/Taxol cells; Lung; Homo sapiens (Human); CVCL_W218
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay; Transwell Invasion assay
• Mechanism Description: ANRIL, also known as CDkN2B antisense RNA1, was origi.lly identified in the familial melanoma patients, it is located within the CDkN2B-CDkN2A gene cluster at chromosome 9p21. ANRIL decreases Bcl-2 expression and increases PARP expression.

Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [1]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Resistant Drug: Paclitaxel
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: A549/Taxol cells; Lung; Homo sapiens (Human); CVCL_W218
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay; Transwell Invasion assay
• Mechanism Description: ANRIL functioning as a potential oncogene was up-regulated in LAD, and promoted the acquisition of chemo-resistance in paclitaxel partly through the mitochondrial pathway by modulating the expression of apoptosis-related protein cleaved-PARP and Bcl-2. ANRIL decreases Bcl-2 expression and increases PARP expression.

Beta-elemene

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Esophageal squamous cell carcinoma [ICD-11: 2B70.3] [2], [3]

• Resistant Disease: Esophageal squamous cell carcinoma [ICD-11: 2B70.3]
• Resistant Drug: Beta-elemene
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: ECA-109 cells; Esophagus; Homo sapiens (Human); CVCL_6898
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Beta-Elemene inhibits the proliferation of esophageal squamous cell carcinoma by regulating long noncoding RNA-mediated inhibition of hTERT expression.

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Oral squamous cell carcinoma [ICD-11: 2B6E.0] [4]

• Resistant Disease: Oral squamous cell carcinoma [ICD-11: 2B6E.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Caspase-3 signaling pathway; Activation; hsa04210
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: HSC3 cells; Tongue; Homo sapiens (Human); CVCL_1288
• In Vitro Model: HaCaT cells; Tongue; Homo sapiens (Human); CVCL_0038
• In Vitro Model: OSCC3 cells; Tongue; Homo sapiens (Human); CVCL_L894
• In Vitro Model: SCC4 cells; Tongue; Homo sapiens (Human); CVCL_1684
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Midkine derived from cancer-associated fibroblasts promotes cisplatin-resistance via up-regulation of the expression of LncRNA ANRIL in tumour cells. ANRIL knockdown overcomes Mk-induced cisplatin resistance via activation of caspase-3-dependent apoptosis. Overexpression of LncRNA ANRIL promots the up-regulation of ABC family proteins MRP1 and ABCC2, which ultimately results in tumour cell resistance to cisplatin.

Disease Class: Nasopharyngeal carcinoma [ICD-11: 2B6B.0] [5]

• Resistant Disease: Nasopharyngeal carcinoma [ICD-11: 2B6B.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Angiogenic potential; Inhibition; hsa04370
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Tumorigenic properties; Inhibition; hsa05200
• In Vitro Model: 5-8F cells; Nasopharynx; Homo sapiens (Human); CVCL_C528
• In Vitro Model: CNE2 cells; Nasopharynx; Homo sapiens (Human); CVCL_6889
• In Vitro Model: CNE1 cells; Throat; Homo sapiens (Human); CVCL_6888
• In Vitro Model: HONE1 cells; Throat; Homo sapiens (Human); CVCL_8706
• In Vitro Model: NP69 cells; Nasopharynx; Homo sapiens (Human); CVCL_F755
• In Vitro Model: S18 cells; Nasopharynx; Homo sapiens (Human); CVCL_B0U9
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTT assay; Annexin V-FITC apoptosis assay
• Mechanism Description: ANRIL directly interacts with let-7a and regulates its expression, ANRIL could directly bind to let-7a and negatively regulate let-7a expression. Down-regulation of LncRNA ANRIL represses tumorigenicity and enhances cisplatin-induced cytotoxicity via regulating microRNA let-7a in nasopharyngeal carcinoma.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Osteosarcoma [ICD-11: 2B51.0] [6]

• Sensitive Disease: Osteosarcoma [ICD-11: 2B51.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell colony; Inhibition; hsa05200
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: MG63 cells; Bone marrow; Homo sapiens (Human); CVCL_0426
• In Vitro Model: SAOS-2 cells; Bone marrow; Homo sapiens (Human); CVCL_0548
• In Vitro Model: U2OS cells; Bone; Homo sapiens (Human); CVCL_0042
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: ANRIL-silenced cells were more sensitive to cisplatin and the expression level of miR-125a-5p was elevated in ANRIL-silenced cells.

Fluorouracil

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Colorectal cancer [ICD-11: 2B91.1] [7]

• Resistant Disease: Colorectal cancer [ICD-11: 2B91.1]
• Resistant Drug: Fluorouracil
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: HT29 Cells; Colon; Homo sapiens (Human); CVCL_A8EZ
• In Vitro Model: SW480 cells; Colon; Homo sapiens (Human); CVCL_0546
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vitro Model: RkO cells; Colon; Homo sapiens (Human); CVCL_0504
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Colony formation assay; Transwell assays and wound healing assay; Flow cytometry assay
• Mechanism Description: ANRIL promotes chemoresistance via disturbing expression of ABCC1 by regulating the expression of Let-7a in colorectal cancer.

Investigative Drug(s) 1 drug(s) in total

Tanshinone IIA

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Age-related nuclear cataract [ICD-11: 9B10.0Y] [8]

• Resistant Disease: Age-related nuclear cataract [ICD-11: 9B10.0Y]
• Resistant Drug: Tanshinone IIA
• Molecule Alteration: Up-regulation; Expression
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SRA01/04 cells; Eye; Homo sapiens (Human); CVCL_7157
• Experiment for Molecule Alteration: Mimic assay; qRT-PCR; Knockdown assay; Western bloting analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay; Carboxy-H2DCFDA assay
• Mechanism Description: Tanshinone IIA protects lens epithelial cells from H2 O 2 -induced injury by upregulation of LncRNA ANRIL.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Esophageal cancer [ICD-11: 2B70]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Esophagus
• The Specified Disease: Esophageal carcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 9.71E-33; Fold-change: -2.76E-01

Colorectal cancer [ICD-11: 2B91]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Rectum
• The Specified Disease: Rectum adenocarcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.19E-21; Fold-change: 7.74E-01

Lung cancer [ICD-11: 2C25]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Lung
• The Specified Disease: Lung adenocarcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 8.07E-05; Fold-change: -9.27E-02
• The Studied Tissue: Lung
• The Specified Disease: Lung squamous cell carcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.79E-16; Fold-change: -1.71E-01

References

• Ref 1: The long noncoding RNA ANRIL acts as an oncogene and contributes to paclitaxel resistance of lung adenocarcinoma A549 cells. Oncotarget. 2017 Jun 13;8(24):39177-39184. doi: 10.18632/oncotarget.16640.
• Ref 2: Beta-Elemene inhibits the proliferation of esophageal squamous cell carcinoma by regulating long noncoding RNA-mediated inhibition of hTERT expression. Anticancer Drugs. 2015 Jun;26(5):531-9. doi: 10.1097/CAD.0000000000000216.
• Ref 3: Long non-coding RNAs in esophageal cancer: molecular mechanisms, functions, and potential applications. J Hematol Oncol. 2018 Sep 17;11(1):118. doi: 10.1186/s13045-018-0663-8.
• Ref 4: Midkine derived from cancer-associated fibroblasts promotes cisplatin-resistance via up-regulation of the expression of lncRNA ANRIL in tumour cells. Sci Rep. 2017 Nov 24;7(1):16231. doi: 10.1038/s41598-017-13431-y.
• Ref 5: Downregulation of lncRNA ANRIL represses tumorigenicity and enhances cisplatin-induced cytotoxicity via regulating microRNA let-7a in nasopharyngeal carcinoma. J Biochem Mol Toxicol. 2017 Jul;31(7). doi: 10.1002/jbt.21904. Epub 2017 Jan 24.
• Ref 6: Effect of lncRNA ANRIL knockdown on proliferation and cisplatin chemoresistance of osteosarcoma cells in vitro. Pathol Res Pract. 2019 May;215(5):931-938. doi: 10.1016/j.prp.2019.01.042. Epub 2019 Jan 30.
• Ref 7: ANRIL promotes chemoresistance via disturbing expression of ABCC1 by regulating the expression of Let-7a in colorectal cancer. Biosci Rep. 2018 Nov 20;38(6):BSR20180620. doi: 10.1042/BSR20180620. Print 2018 Dec 21.
• Ref 8: Tanshinone IIA protects lens epithelial cells from H(2) O (2) -induced injury by upregulation of lncRNA ANRILJ Cell Physiol. 2019 Jan 30. doi: 10.1002/jcp.28189. Online ahead of print.