Molecule Information

General Information of the Molecule (ID: Mol01259)

• Name: LncRNA regulator of Akt signaling associated with HCC and RCC (LNCARSR) ,Homo sapiens
• Synonyms: LNCARSR
• Molecule Type: LncRNA
• Gene Name: C7orf40, FLJ38860, Linc-Myo1g, MYO1GUT
• Gene ID: 102723932
• Location: chr9:79505804-79567802[-]
• Ensembl ID: ENSG00000233086
• HGNC ID: HGNC:53864

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

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Hepatocellular carcinoma [1]

• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: SMMC7721 cells; Uterus; Homo sapiens (Human); CVCL_0534
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: TUNEL assays
• Mechanism Description: lncARSR physically associates with PTEN mRNA, promotes PTEN mRNA degradation, decreases PTEN expression, and activates PI3k/Akt pathway. Upregulated lncARSR promotes doxorubicin resistance in HCC via modulating PTEN-PI3k/Akt pathway.

Sorafenib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Liver cancer [2]

• Sensitive Disease: Liver cancer [ICD-11: 2C12.6]
• Sensitive Drug: Sorafenib
• 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 viability; Inhibition; hsa05200
• Cell Pathway Regulation: STAT3 signaling pathway; Inhibition; hsa04550
• In Vitro Model: HCCLM3 cells; Liver; Homo sapiens (Human); CVCL_6832
• In Vitro Model: SMMC7721 cells; Uterus; Homo sapiens (Human); CVCL_0534
• In Vivo Model: NOD-SCID mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: Interference lncARSR suppressed liver CSCs expansion and the phosphorylation of the STAT3 molecule was evidently inactivated in both the SMMC7721 si-lncARSR and HCCLM3 si-lncARSR cells.

Sunitinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Renal cell carcinoma [3]

• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: ERK signaling pathway; Regulation; hsa04210
• Cell Pathway Regulation: STAT3/AKT signaling pathway; Regulation; hsa04550
• In Vitro Model: 771R-luc cells; Kidney; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qPCR; Northern blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Exosome-Transmitted lncARSR Promotes Sunitinib Resistance in Renal Cancer by Acting as a Competing Endogenous RNA. Here we identified an LncRNA, named lncARSR (LncRNA Activated in RCC with Sunitinib Resistance), which correlated with clinically poor sunitinib response. lncARSR promoted sunitinib resistance via competitively binding miR-34/miR-449 to facilitate AXL and c-MET expression in RCC cells. Furthermore, bioactive lncARSR could be incorporated into exosomes and transmitted to sensitive cells, thus disseminating sunitinib resistance. Treatment of sunitinib-resistant RCC with locked nucleic acids targeting lncARSR or an AXL/c-MET inhibitor restored sunitinib response.

Temozolomide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Glioblastoma [4]

• Resistant Disease: Glioblastoma [ICD-11: 2A00.02]
• Resistant Drug: Temozolomide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: c-Met signaling signaling pathway; Inhibition; hsa01521
• In Vitro Model: HG7 cells; Brain; Homo sapiens (Human); N.A.
• In Vitro Model: LN229 cells; Brain; Homo sapiens (Human); CVCL_0393
• In Vivo Model: BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; Colony formation assay; Flow cytometry assay
• Mechanism Description: Lnc-TALC promotes O6-methylguanine-DNA methyltransferase expression via regulating the c-Met pathway by competitively binding with miR-20b-3p.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Brain cancer [ICD-11: 2A00]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Brain
• The Specified Disease: Brain lower grade glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.44E-01; Fold-change: 6.33E-02
• The Studied Tissue: Brain
• The Specified Disease: Glioblastoma multiforme
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.30E-07; Fold-change: -2.33E-01

Liver cancer [ICD-11: 2C12]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Liver
• The Specified Disease: Liver hepatocellular carcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.27E-01; Fold-change: -5.60E-02

Kidney cancer [ICD-11: 2C90]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Kidney
• The Specified Disease: Kidney clear cell carcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.63E-01; Fold-change: 1.31E-01
• The Studied Tissue: Kidney
• The Specified Disease: Kidney papillary cell carcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.63E-01; Fold-change: 1.62E-01

References

• Ref 1: Long Noncoding RNA lncARSR Promotes Doxorubicin Resistance in Hepatocellular Carcinoma via Modulating PTEN-PI3K/Akt Pathway. J Cell Biochem. 2017 Dec;118(12):4498-4507. doi: 10.1002/jcb.26107. Epub 2017 Jun 9.
• Ref 2: lncARSR promotes liver cancer stem cells expansion via STAT3 pathway. Gene. 2019 Mar 1;687:73-81. doi: 10.1016/j.gene.2018.10.087. Epub 2018 Oct 31.
• Ref 3: Exosome-Transmitted lncARSR Promotes Sunitinib Resistance in Renal Cancer by Acting as a Competing Endogenous RNA. Cancer Cell. 2016 May 9;29(5):653-668. doi: 10.1016/j.ccell.2016.03.004. Epub 2016 Apr 21.
• Ref 4: Lnc-TALC promotes O(6)-methylguanine-DNA methyltransferase expression via regulating the c-Met pathway by competitively binding with miR-20b-3p. Nat Commun. 2019 May 3;10(1):2045. doi: 10.1038/s41467-019-10025-2.