Source 1primary paper2020UNC Libraries
Toolkit/inducible RNAi depletion of CIB1
inducible RNAi depletion of CIB1
Also known as: CIB1 knockdown
Taxonomy: Technique Branch / Method. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Inducible RNAi depletion of CIB1 is a conditional gene-silencing method used in vitro and in vivo to reduce expression of calcium- and integrin-binding protein 1 (CIB1). In triple-negative breast cancer models, CIB1 knockdown impaired cell survival, altered transcriptional programs linked to reduced proliferation and increased cell death, and caused marked shrinkage of MDA-MB-468 xenograft tumors.
Usefulness & Problems
Why this is useful
This method is useful for probing CIB1 dependency in cancer models under controlled induction conditions in both cultured cells and xenografts. The reported data indicate utility for identifying triple-negative breast cancer contexts in which CIB1 loss compromises survival, particularly those associated with elevated AKT activation and low PTEN expression.
Problem solved
It addresses the problem of experimentally reducing CIB1 expression in a temporally controlled manner to test whether tumor cells and tumors depend on CIB1 for survival and growth. In the cited triple-negative breast cancer study, this enabled assessment of both in vitro cell viability effects and in vivo tumor-growth consequences.
Problem links
Need conditional control of signaling activity
DerivedInducible RNAi depletion of CIB1 is a gene-silencing method used in vitro and in vivo to reduce expression of the calcium- and integrin-binding protein 1 (CIB1). In triple-negative breast cancer models, CIB1 knockdown was used to impair cell survival and suppress xenograft tumor growth.
Need conditional recombination or state switching
DerivedInducible RNAi depletion of CIB1 is a gene-silencing method used in vitro and in vivo to reduce expression of the calcium- and integrin-binding protein 1 (CIB1). In triple-negative breast cancer models, CIB1 knockdown was used to impair cell survival and suppress xenograft tumor growth.
Taxonomy & Function
Primary hierarchy
Technique Branch
Method: A concrete method used to build, optimize, or evolve an engineered system.
Techniques
No technique tags yet.
Target processes
recombinationsignalingImplementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedoperating role: builder
The available evidence states that inducible RNAi depletion of CIB1 was implemented in vitro and in vivo, including xenograft experiments. Practical construct details such as promoter system, RNAi trigger design, delivery modality, and induction conditions are not specified in the supplied evidence.
The supplied evidence is confined to triple-negative breast cancer models and does not establish performance in other cell types, diseases, or organisms. The exact RNAi format, induction system, knockdown efficiency, and off-target characterization are not provided in the evidence. Independent replication is not documented in the supplied material.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Observations
successMammalian Cell Lineapplication demo
Inferred from claim c1 during normalization. CIB1 depletion caused significant cell death in 8 of 11 triple-negative breast cancer cell lines tested. Derived from claim c1. Quoted text: CIB1 depletion resulted in significant cell death in 8 of 11 TNBC cell lines tested.
Source:
responsive cell lines(8 of 11)
successMouseapplication demoMDA-MB-468 xenograft
Inferred from claim c3 during normalization. CIB1 knockdown caused dramatic shrinkage of MDA-MB-468 xenograft tumors in vivo. Derived from claim c3. Quoted text: Furthermore, CIB1 knockdown caused dramatic shrinkage of MDA-MB-468 xenograft tumors in vivo.
Source:
successMammalian Cell Lineapplication demo
Inferred from claim c4 during normalization. CIB1 depletion in triple-negative breast cancer cells activated gene programs associated with decreased proliferation and increased cell death. Derived from claim c4. Quoted text: RNA sequence analysis also showed that CIB1 depletion in TNBC cells activates gene programs associated with decreased proliferation and increased cell death.
Source:
Supporting Sources
Ranked Claims
CIB1 depletion caused significant cell death in 8 of 11 triple-negative breast cancer cell lines tested.
CIB1 depletion resulted in significant cell death in 8 of 11 TNBC cell lines tested.
responsive cell lines 8 of 11
Elevated AKT activation status and low PTEN expression predicted sensitivity to CIB1 depletion in triple-negative breast cancer models.
Analysis of components related to PI3K–AKT and RAF–MEK–ERK signaling revealed that elevated AKT activation status and low PTEN expression were key predictors of sensitivity to CIB1 depletion.
CIB1 depletion in triple-negative breast cancer cells activated gene programs associated with decreased proliferation and increased cell death.
RNA sequence analysis also showed that CIB1 depletion in TNBC cells activates gene programs associated with decreased proliferation and increased cell death.
CIB1 knockdown caused dramatic shrinkage of MDA-MB-468 xenograft tumors in vivo.
Furthermore, CIB1 knockdown caused dramatic shrinkage of MDA-MB-468 xenograft tumors in vivo.
Approval Evidence
1 source4 linked approval claimsfirst-pass slug inducible-rnai-depletion-of-cib1
Methods utilized include inducible RNAi depletion of CIB1 in vitro and in vivo
Source:
dependency for cell survivalsupports
CIB1 depletion caused significant cell death in 8 of 11 triple-negative breast cancer cell lines tested.
CIB1 depletion resulted in significant cell death in 8 of 11 TNBC cell lines tested.
Source:
predictor of sensitivitysupports
Elevated AKT activation status and low PTEN expression predicted sensitivity to CIB1 depletion in triple-negative breast cancer models.
Analysis of components related to PI3K–AKT and RAF–MEK–ERK signaling revealed that elevated AKT activation status and low PTEN expression were key predictors of sensitivity to CIB1 depletion.
Source:
transcriptional program changesupports
CIB1 depletion in triple-negative breast cancer cells activated gene programs associated with decreased proliferation and increased cell death.
RNA sequence analysis also showed that CIB1 depletion in TNBC cells activates gene programs associated with decreased proliferation and increased cell death.
Source:
tumor growth impairmentsupports
CIB1 knockdown caused dramatic shrinkage of MDA-MB-468 xenograft tumors in vivo.
Furthermore, CIB1 knockdown caused dramatic shrinkage of MDA-MB-468 xenograft tumors in vivo.
Source:
Comparisons
Source-backed strengths
CIB1 depletion caused significant cell death in 8 of 11 triple-negative breast cancer cell lines tested, indicating activity across multiple models. Sensitivity was associated with elevated AKT activation and low PTEN expression, and knockdown also induced transcriptional programs consistent with decreased proliferation and increased cell death. In vivo, CIB1 knockdown produced dramatic shrinkage of MDA-MB-468 xenograft tumors.
inducible RNAi depletion of CIB1 and experimental pipeline for creating designer Nodal signaling patterns address a similar problem space because they share recombination, signaling.
Shared frame: same top-level item type; shared target processes: recombination, signaling
Strengths here: looks easier to implement in practice.
Compared with Opto-RhoGEFs
inducible RNAi depletion of CIB1 and Opto-RhoGEFs address a similar problem space because they share recombination, signaling.
Shared frame: shared target processes: recombination, signaling
Strengths here: looks easier to implement in practice.
Compared with shRNA-delivered by lentivirus
inducible RNAi depletion of CIB1 and shRNA-delivered by lentivirus address a similar problem space because they share recombination.
Shared frame: same top-level item type; shared target processes: recombination; shared mechanisms: rna interference
Strengths here: looks easier to implement in practice.
Ranked Citations
- 1.