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Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis III

ABSTRACT: Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis III

PROVIDER: PRJNA756304 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15530060_1.fastq.gz	Fastqsanger.gz
	SRR15530060_2.fastq.gz	Fastqsanger.gz
	SRR15530061_1.fastq.gz	Fastqsanger.gz
	SRR15530061_2.fastq.gz	Fastqsanger.gz
	SRR15530062_1.fastq.gz	Fastqsanger.gz

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Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis

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Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis II

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Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis I

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Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis III

Project description:The treatment of colorectal cancer (CRC) is an unmet medical need in absence of early diagnosis. Here, upon characterizing cancer-specific transposable element-driven transpochimeric gene transcripts (TcGTs) produced by this tumor, we found that expression of the hominid-restricted retrogene POU5F1B through aberrant activation of a primate-specific endogenous retroviral promoter is a strong negative prognostic CRC biomarker. Correlating this observation, we could demonstrate that POU5F1B fosters the proliferation and metastatic potential of CRC cells. We further determined that POU5F1B, in spite of its phylogenetic relationship with the POU5F1/OCT4 transcription factor, is a membrane-enriched protein that associates with protein kinases and known targets or interactors as well as with cytoskeleton-related molecules, and induces intracellular signaling events and the release of trans-acting factors involved in cell growth and cell adhesion. As POU5F1B is an apparently non-essential gene only lowly expressed in normal tissues, and as POU5F1B-containing TcGTs are detected in other tumors besides CRC, our data provide interesting leads for the development of cancer therapies.

2022-08-02 | GSE182466 | GEO

Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis

Project description:The treatment of colorectal cancer (CRC) is an unmet medical need in absence of early diagnosis. Here, upon characterizing cancer-specific transposable element-driven transpochimeric gene transcripts (TcGTs) produced by this tumor in the SYSCOL cohort, we find that expression of the hominid-restricted retrogene POU5F1B through aberrant activation of a primate-specific endogenous retroviral promoter is a strong negative prognostic biomarker. Correlating this observation, we demonstrate that POU5F1B fosters the proliferation and metastatic potential of CRC cells. We further determine that POU5F1B, in spite of its phylogenetic relationship with the POU5F1/OCT4 transcription factor, is a membrane-enriched protein that associates with protein kinases and known targets or interactors as well as with cytoskeleton-related molecules, and induces intracellular signaling events and the release of trans-acting factors involved in cell growth and cell adhesion. As POU5F1B is an apparently non-essential gene only lowly expressed in normal tissues, and as POU5F1B-containing TcGTs are detected in other tumors besides CRC, our data provide interesting leads for the development of cancer therapies. The treatment of colorectal cancer (CRC) is an unmet medical need in absence of early diagnosis. Here, the authors characterise cancer-specific transposable element-driven transpochimeric gene transcripts and highlight the role of POU5F1B in CRC growth and metastasis.

| S-EPMC9392749 | biostudies-literature

Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-08-02 | GSE182467 | GEO

Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis II

2022-08-02 | GSE182465 | GEO

Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis I

Project description:Tumors occasionally express oncogenes via aberrant activation of transposable elements (TE), but a role for this process in oncogenesis was seldom demonstrated. Here, we identify expression of the hominid-restricted retrogene POU5F1B through aberrant activation of an endogenous retroviral promoter as a strong negative prognostic marker in colorectal cancer (CRC). We further determine that POU5F1B is membrane-enriched and interacts with ERBB2 and associated effectors, and fosters the proliferation and metastatic potential of CRC cells through intracellular signaling events and release of trans-acting molecules involved in cell growth, angiogenesis and cell adhesion. As POU5F1B is apparently non-essential and only lowly expressed in normal tissues, and as POU5F1B-containing TE-driven transcripts are detected in other tumors besides CRC, these data provide interesting leads for the development of cancer therapies.

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Expression profiles for lymph node metastasis in I-III colorectal cancer

Project description:Expression profiles for lymph node metastasis in I-III colorectal cancer

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Stage II and stage III colorectal cancer

Project description:Distant metastasis is the major causes of death in colorectal cancer (CRC) patients. In order to identify genes influencing the prognosis of patients with CRC, we compared gene expression in primary tumors with and without distant metastasis using an oligonucleotide microarray. We also examined the expression of the candidate gene in 100 CRC patients by quantitative real-time reverse transcription PCR and studied the relationship between its expression and the prognosis of patients with CRC. As a result, we identified MUC12 as a candidate gene involved in metastasis processes by microarray analysis. Quantitative real-time reverse transcription PCR showed that MUC12 expression was significantly lower in cancer tissues than in adjacent normal tissues (P < 0.001). In stage II and stage III CRC, patients with low expression showed worse disease-free survival (P = 0.038). Multivariate analysis disclosed that MUC12 expression status was an independent prognostic factor in stage II and stage III CRC (relative risk, 9.532; 95% confidence interval, 2.303-41.905; P = 0.002). This study revealed the prognostic value of MUC12 expression in CRC patients. Moreover, our result suggests MUC12 expression is a possible candidate gene for assessing postoperative adjuvant therapy for CRC patients.

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