BCL7C Human

What is BCL7C and how is it genetically characterized?

BCL7C (B-cell CLL/lymphoma 7 protein family member C) is located on chromosome 16p11.2 and shares partial sequence homology with two other family members, BCL7A and BCL7B. While research on BCL7C is still emerging, it has been identified as having significant roles in cancer biology, particularly as a tumor suppressor in ovarian cancer .

Methodological approach: Genomic characterization of BCL7C typically involves sequencing analysis, expression profiling across tissue types, and comparative genomic alignment with other BCL7 family members to identify conserved domains and unique regions.

How does BCL7C expression vary across normal human tissues?

Current research data on BCL7C tissue-specific expression patterns in normal tissues is limited. Understanding BCL7C expression in non-pathological states provides crucial context for interpreting its altered expression in disease.

Methodological approach: Researchers should employ a combination of RNA-seq, immunohistochemistry with validated antibodies, and tissue microarrays to establish comprehensive expression profiles across multiple tissue types.

What evolutionary conservation exists for BCL7C across species?

Methodological approach: Comparative genomic analysis combined with functional assays in multiple model organisms can help delineate conserved versus divergent functions.

What evidence supports BCL7C's role as a tumor suppressor?

Multiple lines of evidence demonstrate BCL7C's tumor suppressor function in ovarian cancer:

• BCL7C is downregulated in human ovarian carcinomas

• Underexpression correlates with poor prognosis

• Ectopic BCL7C restrains proliferation and invasion of ovarian cancer cells

• BCL7C depletion reduces apoptosis while promoting proliferation and invasion

• Primary ovarian carcinomas with low BCL7C levels often show elevated expression of mutant p53 target genes

Methodological approach: To investigate tumor suppressor properties, researchers should employ gain- and loss-of-function experiments in relevant cancer models, coupled with phenotypic assays measuring proliferation, invasion, and apoptosis.

How does BCL7C expression correlate with clinical outcomes in different cancer types?

Underexpression of BCL7C is associated with unfavorable prognosis in ovarian cancer and several other human cancers, suggesting its potential utility as a prognostic biomarker across multiple cancer contexts .

Methodological approach: Kaplan-Meier survival analysis stratified by BCL7C expression levels, multivariate Cox regression analysis controlling for known prognostic factors, and meta-analysis across multiple cancer datasets are recommended approaches.

How does BCL7C function compare to other BCL7 family members in cancer?

While BCL7C appears to function as a tumor suppressor in ovarian cancer, research on BCL7B suggests potentially oncogenic roles in some cancer contexts. BCL7B has been identified as having high diagnostic and prognostic value in pan-cancer analysis .

Methodological approach: Comparative functional studies with simultaneous manipulation of multiple family members, followed by comprehensive phenotypic and transcriptomic profiling.

How does BCL7C interact with the p53 pathway?

BCL7C suppresses mutant p53-mediated gene transcription by directly binding to mutant p53. Knockdown of BCL7C enhances the expression of mutant p53 target genes in ovarian cancer cells. This mechanism appears central to BCL7C's tumor suppressor function .

Methodological approach: Protein-protein interaction studies (co-immunoprecipitation, proximity ligation assays), ChIP-seq to identify genomic binding sites, and reporter assays to quantify transcriptional effects.

Is BCL7C's tumor suppressor activity dependent on p53 status?

Yes, current evidence indicates a p53-dependent mechanism. BCL7C abrogates mutant p53-induced cell proliferation and invasion but shows no impact on proliferation and invasion of cancer cells with depleted p53 or those harboring wild-type p53 .

Methodological approach: Isogenic cell line models with varying p53 status (wild-type, mutant, null) combined with BCL7C manipulation provide the most controlled experimental system to test this dependency.

What epigenetic mechanisms might regulate BCL7C expression?

While direct evidence for BCL7C epigenetic regulation is limited in the provided search results, research in the field of epigenetics suggests potential regulatory mechanisms including DNA methylation, histone modifications, and chromatin accessibility .

Methodological approach: Integrated epigenomic analysis combining DNA methylation profiling, ChIP-seq for histone marks, ATAC-seq for chromatin accessibility, and correlation with expression data.

What CRISPR-based strategies are most effective for studying BCL7C function?

For CRISPR-based functional studies of BCL7C:

• Use guide RNA sequences designed to efficiently target the BCL7C gene with minimal off-target effects

• Order at least two gRNA constructs per gene to increase success rates

• Verify gRNA sequences against your target gene sequence before ordering

• Consider the specific splice variants or exons you wish to target

Methodological approach: Careful gRNA design with off-target prediction algorithms, validation of editing efficiency, and phenotypic confirmation across multiple independent clones.

What cellular assays best capture BCL7C's tumor suppressor activity?

Based on BCL7C's known functions, researchers should consider:

• Proliferation assays (BrdU incorporation, Ki-67 staining)

• Invasion assays (transwell, 3D spheroid invasion)

• Apoptosis assays (Annexin V, caspase activation)

• Gene expression analysis of mutant p53 target genes

• Protein-protein interaction studies focused on p53 binding

Methodological approach: Multi-parametric approach combining real-time monitoring systems with endpoint assays to capture the dynamic nature of these cellular processes.

How can researchers distinguish between direct and indirect effects of BCL7C manipulation?

This represents a significant challenge in BCL7C research, particularly given its role in regulating transcription through mutant p53.

Methodological approach: Acute versus chronic depletion/overexpression systems, rescue experiments, and temporal analysis of molecular changes can help distinguish primary from secondary effects.

How might chromatin context influence BCL7C function?

Given that BCL7C interacts with mutant p53, which acts as a transcription factor, and considering the importance of chromatin remodeling in cancer (as seen with SMARCA4/BRG1 ), the chromatin context likely influences BCL7C function.

Methodological approach: Combining ChIP-seq for BCL7C and mutant p53 with ATAC-seq and histone modification mapping in the same cellular contexts can provide insights into how chromatin states affect BCL7C activity.

What is the relationship between BCL7C and DNA replication stress responses?

While not directly addressed for BCL7C in the search results, research on SMARCA4/BRG1 has shown connections between chromatin remodeling factors and replication stress response . Similar relationships might exist for BCL7C.

Methodological approach: DNA fiber analysis, γH2AX foci quantification, and cell synchronization studies in BCL7C-manipulated cells during replication stress conditions.

How do post-translational modifications regulate BCL7C activity?

Post-translational modifications often regulate protein function, stability, and interactions, but specific information about BCL7C modifications is limited in current research.

Methodological approach: Mass spectrometry-based proteomics focused on identifying phosphorylation, ubiquitination, acetylation, and other modifications under various cellular conditions.

How might BCL7C status be incorporated into cancer prognostic models?

Given BCL7C's association with prognosis in multiple cancer types, particularly ovarian cancer, integration into prognostic models represents a valuable research direction.

Methodological approach: Development of multi-factor prognostic signatures incorporating BCL7C expression with other established biomarkers, validated in independent patient cohorts using appropriate statistical methods.

What therapeutic strategies might leverage BCL7C biology?

Potential therapeutic approaches could include:

• Restoration of BCL7C expression or function in cancers with downregulation

• Combinatorial approaches targeting both BCL7C and mutant p53 pathways

• Identification of synthetic lethal interactions in BCL7C-deficient contexts

Methodological approach: High-throughput drug screening in isogenic cell line pairs differing only in BCL7C status, followed by validation in patient-derived models.

How can patient stratification based on BCL7C status improve clinical trial design?

Incorporating BCL7C status in clinical trial design could enhance the identification of responsive patient subgroups, particularly in cancers where BCL7C has prognostic significance.

Methodological approach: Retrospective analysis of existing trial data stratified by BCL7C expression, followed by prospective trials with pre-specified BCL7C-based subgroup analyses.

What are the relative advantages of various model systems for BCL7C research?

Different model systems offer distinct advantages:

Methodological approach: Multi-model validation of key findings across different systems to ensure robustness and translational relevance.

How do technological approaches for BCL7C detection compare?

Various techniques offer different insights into BCL7C biology:

Methodological approach: Integration of complementary techniques to build a comprehensive view of BCL7C biology at multiple levels.

What bioinformatic approaches best reveal BCL7C's role in multi-omics datasets?

Multi-omics integration is essential for comprehensive understanding of BCL7C function.

Methodological approach: Network-based integration of transcriptomic, proteomic, and epigenomic data using algorithms designed to identify causal relationships rather than mere correlations.

What are the most critical knowledge gaps in BCL7C research?

Key knowledge gaps include:

• Comprehensive normal tissue expression patterns

• BCL7C regulation at transcriptional and post-transcriptional levels

• Functions beyond p53 interaction

• Role in non-ovarian cancers

• Potential as a therapeutic target

Methodological approach: Systematic literature review and meta-analysis to identify inconsistencies and unexplored areas, followed by targeted experimental approaches.

How might single-cell technologies advance BCL7C research?

Single-cell approaches could reveal heterogeneity in BCL7C expression and function within tumors that is missed by bulk analysis.

Methodological approach: Single-cell RNA-seq, CyTOF, and spatial transcriptomics in tumor samples to map BCL7C expression patterns in relation to cell states and microenvironmental features.