Molecule Information

General Information of the Molecule (ID: Mol01220)

• Name: Cancer susceptibility 2 (CASC2) ,Homo sapiens
• Synonyms: C20orf199; HSUP1; HSUP2; NCRNA00275; ZNFX1-AS1; C10orf5
• Molecule Type: LncRNA
• Gene Name: CASC2
• Gene ID: 255082
• Location: chr10:118046279-118210158[+]
• Ensembl ID: ENSG00000177640
• HGNC ID: HGNC:22933

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) 5 drug(s) in total

Berberine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Colorectal cancer [1]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Sensitive Drug: Berberine
• 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 viability; Inhibition; hsa05200
• In Vitro Model: HT29 Cells; Colon; Homo sapiens (Human); CVCL_A8EZ
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: LncRNA CASC2 mediates the berberine-induced pro-apoptotic effect via inhibition of Bcl-2 expression at the post-transcriptional level.

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Gastric cancer [2]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Down-regulation of CASC2 contributes to cisplatin resistance in gastric cancer by elevating miR-19a expression.

Disease Class: Cervical cancer [3]

• Resistant Disease: Cervical cancer [ICD-11: 2C77.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: Siha cells; Cervix uteri; Homo sapiens (Human); CVCL_0032
• In Vitro Model: Caski cells; Uterus; Homo sapiens (Human); CVCL_1100
• In Vitro Model: ME-180 cells; Uterus; Homo sapiens (Human); CVCL_1401
• In Vitro Model: H8 cells; Uterus; Homo sapiens (Human); CVCL_9389
• In Vitro Model: HCE1 cells; Uterus; Homo sapiens (Human); CVCL_A8SM
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: CASC2 upregulated PTEN expression by direct inhibiting miR21 in the DDP-resistant cancer cells, leading to the down-regulation of p-AkT protein, CASC2 up-regulates PTEN as a ceRNA of miR21. Inhibiting miR21 increased the sensitivity of human glioblastoma cells U251 and LN229 to taxol.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Non-small cell lung cancer [4]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: ERK1/2 and Beta-catenin signaling pathway; Inhibition; hsa04210
• In Vitro Model: H226 Cells; Lung; Homo sapiens (Human); CVCL_1544
• In Vitro Model: H292 cells; Lung; Homo sapiens (Human); CVCL_0455
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Increasing the CASC2c expression level could reverse the resistance of NSCLC cells to cisplatin.

Disease Class: Cervical cancer [3]

• Sensitive Disease: Cervical cancer [ICD-11: 2C77.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: PTEN signaling pathway; Activation; hsa05235
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: Siha cells; Cervix uteri; Homo sapiens (Human); CVCL_0032
• In Vitro Model: Caski cells; Uterus; Homo sapiens (Human); CVCL_1100
• In Vitro Model: ME-180 cells; Uterus; Homo sapiens (Human); CVCL_1401
• In Vitro Model: H8 cells; Uterus; Homo sapiens (Human); CVCL_9389
• In Vitro Model: HCE1 cells; Uterus; Homo sapiens (Human); CVCL_A8SM
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: CASC2 upregulated PTEN expression by direct inhibiting miR21 in the DDP-resistant cancer cells, leading to the down-regulation of p-AkT protein, CASC2 up-regulates PTEN as a ceRNA of miR21. Inhibiting miR21 increased the sensitivity of human glioblastoma cells U251 and LN229 to taxol.

Docetaxel

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Prostate cancer [5]

• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Sensitive Drug: Docetaxel
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: ERK signaling pathway; Regulation; hsa04210
• Cell Pathway Regulation: RTK signaling pathway; Inhibition; hsa04015
• In Vitro Model: DU-145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: LNCaP cells; Prostate; Homo sapiens (Human); CVCL_0395
• In Vitro Model: PC3 cells; Prostate; Homo sapiens (Human); CVCL_0035
• In Vitro Model: RWPE-1 cells; Prostate; Homo sapiens (Human); CVCL_3791
• In Vitro Model: C4-2 cells; Prostate; Homo sapiens (Human); CVCL_4782
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay; Flow cytometer assay
• Mechanism Description: CASC2 directly targets miR183 to inhibit its expression. SPRY2 is regarded as a negative regulator RTk signaling pathway, antagonizing cell migration and/or cellular differentiation occurring through the ERk signaling. CASC2 competes with SPRY2 for miR183 binding to rescue the expression of SPRY2 in PC cells, thus suppressing the cell proliferation and promoting the apoptosis of PC cells, finally enhancing PC cells chemo-sensitivity to docetaxel through SPRY2 downstream ERk signaling pathway.

Sanguinarine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Epithelial ovarian cancer [6]

• Resistant Disease: Epithelial ovarian cancer [ICD-11: 2B5D.0]
• Resistant Drug: Sanguinarine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: Cell viability; Activation; hsa05200
• Cell Pathway Regulation: NF-kB signaling pathway; Activation; hsa04218
• Cell Pathway Regulation: PI3K/AKT/mTOR signaling pathway; Activation; hsa04151
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: OVCAR3 cells; Ovary; Homo sapiens (Human); CVCL_0465
• In Vitro Model: HO8910 cells; Ovary; Homo sapiens (Human); CVCL_6868
• In Vitro Model: CAOV3 cells; Ovary; Homo sapiens (Human); CVCL_0201
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Transwell assay; Flow cytometry assay
• Mechanism Description: Sanguinarine exhibits antitumor effects in epithelial ovarian cancer cells possible via regulating CASC2-EIF4A3 axis and/or inhibiting NF-kB signaling or PI3k/AkT/mTOR pathway and IF4A3 was identified as a CASC2 binding protein, and knockdown of EIF4A3 further reversed the effects of sanguinarine plus CASC2 silencing.

Temozolomide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Malignant glioma [7], [8]

• Resistant Disease: Malignant glioma [ICD-11: 2A00.2]
• Resistant Drug: Temozolomide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: DNA damage repair signaling pathway; Activation; hsa03410
• In Vitro Model: U87 cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vitro Model: U257 cells; Brain; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: Flow cytometry assay; MTT assay; Transwell assay
• Mechanism Description: Upregulation of CASC2 sensitized glioma to temozolomide cytotoxicity through autophagy inhibition by sponging miR193a-5p and regulating mTOR expression. CASC2 is downregulated in gliomas, resulting in increased miR193a-5p level and a decrease in mTOR expression, which further induces protective autophagy, leading to TMZ resistance.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Glioma [8]

• Sensitive Disease: Glioma [ICD-11: 2A00.1]
• Sensitive Drug: Temozolomide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: U87 cells; Brain; Homo sapiens (Human); CVCL_0022
• In Vitro Model: U257 cells; Brain; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: Flow cytometry assay; MTT assay; Transwell assay
• Mechanism Description: CASC2 negatively regulates miR193a-5p expression by direct interaction in glioma cells. Overexpression of CASC2 or inhibition of miR193a-5p reduced TMZ-induced autophagy via mTOR upregulation, which makes the glioma cells become sensitive to TMZ cytotoxicity.

Disease Class: Glioma [7]

• Sensitive Disease: Glioma [ICD-11: 2A00.1]
• Sensitive Drug: Temozolomide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PTEN signaling pathway; Activation; hsa05235
• In Vitro Model: U251 cells; Brain; Homo sapiens (Human); CVCL_0021
• In Vitro Model: LN229 cells; Brain; Homo sapiens (Human); CVCL_0393
• In Vitro Model: SNB19 cells; Brain; Homo sapiens (Human); CVCL_0535
• In Vitro Model: U373 cells; Brain; Homo sapiens (Human); CVCL_2219
• In Vitro Model: U118 cells; Brain; Homo sapiens (Human); CVCL_0633
• In Vitro Model: NHA cells; Brain; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay; BrdU incorporation assay
• Mechanism Description: LncRNA CASC2 interacts with miR181a to modulate glioma growth and resistance to TMZ through PTEN pathway.

Disease Class: Malignant glioma [7]

• Sensitive Disease: Malignant glioma [ICD-11: 2A00.2]
• Sensitive Drug: Temozolomide
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell growth; Inhibition; hsa05200
• In Vitro Model: U251 cells; Brain; Homo sapiens (Human); CVCL_0021
• In Vitro Model: LN229 cells; Brain; Homo sapiens (Human); CVCL_0393
• In Vitro Model: SNB19 cells; Brain; Homo sapiens (Human); CVCL_0535
• In Vitro Model: U373 cells; Brain; Homo sapiens (Human); CVCL_2219
• In Vitro Model: U118 cells; Brain; Homo sapiens (Human); CVCL_0633
• In Vitro Model: NHA cells; Brain; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: MTT assay; BrdU incorporation assay
• Mechanism Description: CASC2 up-regulated PTEN protein and down-regulated p-AkT protein through regulating miR181a, and the effect of CASC2 on PTEN and p-AkT could be partially restored by miR181a.

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

Cisplatinum

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Cholangiocarcinoma [9]

• Resistant Disease: Cholangiocarcinoma [ICD-11: 2C12.0]
• Resistant Drug: Cisplatinum
• Molecule Alteration: Down-regulation; Interaction
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Huh7 cells; Kidney; Homo sapiens (Human); CVCL_U442
• In Vitro Model: SMMC-7721 cells; Uterus; Homo sapiens (Human); CVCL_0534
• Experiment for Molecule Alteration: Overexpression assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Overexpression of CASC2 Improves Cisplatin Sensitivity in Hepatocellular Carcinoma Through Sponging miR-222.

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: 4.37E-06; Fold-change: -3.39E-02
• The Studied Tissue: Brain
• The Specified Disease: Glioblastoma multiforme
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 3.34E-07; Fold-change: 6.78E-02

Gastric cancer [ICD-11: 2B72]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Stomach
• The Specified Disease: Stomach adenocarcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.20E-35; Fold-change: -2.40E-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: 7.55E-01; Fold-change: -1.34E-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: 2.12E-06; Fold-change: -7.69E-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: 2.03E-01; Fold-change: -4.80E-02

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: 4.16E-03; Fold-change: 4.15E-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: 9.87E-33; Fold-change: 1.86E-01

Cervical cancer [ICD-11: 2C77]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Cervix uteri
• The Specified Disease: Cervical and endocervical cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.59E-01; Fold-change: 2.19E-02

Prostate cancer [ICD-11: 2C82]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Prostate
• The Specified Disease: Prostate adenocarcinoma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.84E-02; Fold-change: -2.09E-02

References

• Ref 1: Berberine Promotes Apoptosis of Colorectal Cancer via Regulation of the Long Non-Coding RNA (lncRNA) Cancer Susceptibility Candidate 2 (CASC2)/AU-Binding Factor 1 (AUF1)/B-Cell CLL/Lymphoma 2 (Bcl-2) Axis. Med Sci Monit. 2019 Jan 25;25:730-738. doi: 10.12659/MSM.912082.
• Ref 2: Down-regulation of CASC2 contributes to cisplatin resistance in gastric cancer by sponging miR-19a. Biomed Pharmacother. 2018 Dec;108:1775-1782. doi: 10.1016/j.biopha.2018.09.181. Epub 2018 Oct 16.
• Ref 3: Modulation of CASC2/miR-21/PTEN pathway sensitizes cervical cancer to cisplatin. Arch Biochem Biophys. 2017 Jun 1;623-624:20-30. doi: 10.1016/j.abb.2017.05.001. Epub 2017 May 8.
• Ref 4: Effects of long non-coding RNA (lncRNA) cancer susceptibility candidate 2c (CASC2c) on proliferation, metastasis and drug resistance of non-small cell lung cancer (NSCLC) cells through ERK1/2 and Beta-catenin signaling pathways. Pathol Res Pract. 2019 Sep;215(9):152522. doi: 10.1016/j.prp.2019.152522. Epub 2019 Jun 27.
• Ref 5: Long non-coding RNA CASC2 regulates Sprouty2 via functioning as a competing endogenous RNA for miR-183 to modulate the sensitivity of prostate cancer cells to docetaxel. Arch Biochem Biophys. 2019 Apr 15;665:69-78. doi: 10.1016/j.abb.2018.01.013. Epub 2018 Jan 31.
• Ref 6: Sanguinarine inhibits epithelial ovarian cancer development via regulating long non-coding RNA CASC2-EIF4A3 axis and/or inhibiting NF-kB signaling or PI3K/AKT/mTOR pathway. Biomed Pharmacother. 2018 Jun;102:302-308. doi: 10.1016/j.biopha.2018.03.071. Epub 2018 Mar 22.
• Ref 7: LncRNA CASC2 Interacts With miR-181a to Modulate Glioma Growth and Resistance to TMZ Through PTEN Pathway. J Cell Biochem. 2017 Jul;118(7):1889-1899. doi: 10.1002/jcb.25910. Epub 2017 Feb 13.
• Ref 8: Upregulation of CASC2 sensitized glioma to temozolomide cytotoxicity through autophagy inhibition by sponging miR-193a-5p and regulating mTOR expression. Biomed Pharmacother. 2018 Jan;97:844-850. doi: 10.1016/j.biopha.2017.10.146. Epub 2017 Nov 7.
• Ref 9: Overexpression of CASC2 Improves Cisplatin Sensitivity in Hepatocellular Carcinoma Through Sponging miR-222DNA Cell Biol. 2019 Nov;38(11):1366-1373. doi: 10.1089/dna.2019.4882. Epub 2019 Oct 18.