Molecule Information

General Information of the Molecule (ID: Mol01322)

• Name: KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) ,Homo sapiens
• Synonyms: KCNQ1OT1
• Molecule Type: LncRNA
• Gene Name: FOXF1-AS1, lincFOXF1, onco-lncRNA-21
• Gene ID: 10984
• Location: chr11:2608328-2699994[-]
• Ensembl ID: ENSG00000269821
• HGNC ID: HGNC:6295

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) 3 drug(s) in total

Oxaliplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.2] [1]

• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Resistant Drug: Oxaliplatin
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Liver cancer [ICD-11: 2C12]
• The Specified Disease: Cholangiocarcinoma
• The Studied Tissue: Bile duct
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.01E-06; Fold-change: 2.31E+00; Z-score: 5.87E+00
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: miR7-5p/ABCC1 signaling pathway; Regulation; N.A.
• In Vitro Model: Huh-7 cells; Liver; Homo sapiens (Human); CVCL_0336
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: SMMC7721 cells; Uterus; Homo sapiens (Human); CVCL_0534
• In Vitro Model: Skhep1 cells; Liver; Homo sapiens (Human); CVCL_0525
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Overexpression of kCNQ1OT1 enhances OXA resistance through downregulating miR-7-5p and upregulating ABCC1 in HCC cells.

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Tongue cancer [ICD-11: 2B62.0] [2]

• Resistant Disease: Tongue cancer [ICD-11: 2B62.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: Ezrin/FAKT/Src signaling pathway; Activation; hsa05205
• In Vitro Model: CAL27 cells; Oral; Homo sapiens (Human); CVCL_1107
• In Vitro Model: SCC9 cells; Tongue; Homo sapiens (Human); CVCL_1685
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Microarray; RT-PCR
• Experiment for Drug Resistance: MTS assay; EdU assay; Flow cytometric analysis
• Mechanism Description: KCNQ1OT1 promotes TSCC cell proliferation and chemo-resistance via the regulation of miR-211-5p mediated Ezrin/Fak/Src signaling.

Temozolomide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Glioma [ICD-11: 2A00.02] [3]

• Resistant Disease: Glioma [ICD-11: 2A00.02]
• Resistant Drug: Temozolomide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: U251 cells; Brain; Homo sapiens (Human); CVCL_0021
• In Vitro Model: U87 cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR; Dual?Luciferase Assay; Western Blot; qRT?PCR; Immunohistochemical; Immunofluorescence
• Experiment for Drug Resistance: Clonogenicity Assay; Apoptosis Analysis; MTT Assay
• Mechanism Description: The present study demonstrated that the lncRNA KCNQ1OT1 increased in TMZ-resistant glioma cells compared to the TMZ-sensitive cells. The introduction of KCNQ1OT1 promoted cell viability, clonogenicity, and rhodamine 123 efflux while hampering TMZ-induced apoptosis. Moreover, KCNQ1OT1 directly sponged miR-761, which decreased in TMZ-resistant sublines. The overexpression of miR-761 attenuated cell viability and clonogenicity, while triggering apoptosis and rhodamine 123 accumulation post-TMZ exposure, leading to a response to TMZ. The interaction between miR-761 and 3'-untranslated region of PIM1 attenuated PIM1-mediated signaling cascades. Furthermore, the knockdown of KCNQ1OT1 augmented the TMZ-induced tumor regression in TMZ-resistant U251 mouse models. Briefly, the present study evaluated that KCNQ1OT1 conferred TMZ resistance by releasing PIM1 expression from miR-761, resulting in the upregulation of PIM-mediated MDR1, c-Myc, and Survivin. The present findings demonstrated that the interplay of KCNQ1OT1: miR-761: PIM1 regulated chemoresistance in gliomas and provided a promising therapeutic target for TMZ-resistant glioma patients.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Liver cancer [ICD-11: 2C12]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Bile duct
• The Specified Disease: Cholangiocarcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.53E-03; Fold-change: -6.92E-01
• The Studied Tissue: Liver
• The Specified Disease: Liver hepatocellular carcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.11E-24; Fold-change: 4.15E-01

References

• Ref 1: Long non-coding RNA KCNQ1OT1 modulates oxaliplatin resistance in hepatocellular carcinoma through miR-7-5p/ ABCC1 axis. Biochem Biophys Res Commun. 2018 Sep 18;503(4):2400-2406. doi: 10.1016/j.bbrc.2018.06.168. Epub 2018 Jul 4.
• Ref 2: LncRNA KCNQ1OT1 regulates proliferation and cisplatin resistance in tongue cancer via miR-211-5p mediated Ezrin/Fak/Src signaling. Cell Death Dis. 2018 Jul 3;9(7):742. doi: 10.1038/s41419-018-0793-5.
• Ref 3: Indian J Med Paediatr Oncol. 2015 Apr-Jun;36(2):133-6. doi: 10.4103/0971-5851.158852.