Molecule Information

General Information of the Molecule (ID: Mol04450)

• Name: Chkb-as1 ,Homo sapiens
• Synonyms: Chkb-as1
• Molecule Type: LncRNA

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

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Clinical Trial Drug(s) 1 drug(s) in total

Dactolisib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Kidney cancer [ICD-11: 2C90.1] [1]

• Resistant Disease: Kidney cancer [ICD-11: 2C90.1]
• Resistant Drug: Dactolisib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT/mTOR signaling pathway; Activation; hsa04151
• In Vitro Model: 786-O-Res cells; kidney; Homo sapiens (Human); N.A.
• In Vitro Model: Caki-1-Res cells; kidney; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Western blotting and qRT-PCR were employed to examine alterations in signaling pathways, with an animal model providing additional validation. Our results show a marked increase in the IC50 of NVP-BEZ235 in resistant cell lines compared to their parental counterparts. A significant revelation was the role of LncRNA-CHKB-AS1 in mediating drug resistance. We observed dysregulated expression of CHKB-AS1 in both clinical samples of clear cell renal cell carcinoma (ccRCC) and cell lines. In vivo experiments further substantiated our findings, showing that CHKB-AS1 overexpression significantly enhanced tumor growth and resistance to NVP-BEZ235 in a subcutaneous tumorigenesis model, as evidenced by increased tumor volume and weight, whereas CHKB-AS1 knockdown led to a marked reduction in these parameters. Critically, CHKB-AS1 was identified to interact with MAP4, a key regulator in the phosphorylation of the PI3k/Akt/mTOR pathway.

References

• Ref 1: CHKB-AS1 enhances proliferation and resistance to NVP-BEZ235 of renal cancer cells via regulating the phosphorylation of MAP4 and PI3K/AKT/mTOR signaling. Eur J Med Res. 2023 Dec 14;28(1):588.