Prognostic Value of Oct4 in Colorectal Cancer: Analysis Using Immunohistochemistry and Bioinformatics Validation

Fang, Wenjia; Ni, Meilin; Zhang, Mingming; Chen, Hanqing

doi:10.2217/bmm-2020-0069

Cited by 7 publications

(6 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several research groups have published results that emphasize the role of OCT4 in the aggressive behavior of CRC and its contribution to forming liver metastasis in CRC, especially OCT4 in the high-expression group, which is consistent with our results ( 66 – 68 ). Furthermore, OCT4 expression was denoted as an independent prognostic biomarker for predicting worse disease-specific survival and overall survival in CRC ( 69 ). On the other hand, the expression of all OCT4 isoforms in both primary and metastatic samples than in control samples was significantly downregulated.…”

Section: Discussionmentioning

confidence: 99%

Expression of OCT4 isoforms is reduced in primary colorectal cancer

Turyova,

Mikolajcik,

Grendar

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

IntroductionColorectal cancer (CRC) is one of the most common types of cancer worldwide. The carcinogenesis of CRC is indeed complex, and there are many different mechanisms and pathways that contribute to the development of malignancy and the progression from primary to metastatic tumors. The OCT4A, encoded by the POU5F1 gene, is a transcription factor responsible for the phenotype of stem cells, maintaining pluripotency and regulation of differentiation. The POU5F1 gene is made up of five exons that can create numerous isoforms through alternative promoter or alternative splicing. In addition to OCT4A, other isoforms called OCT4B are also translated into protein; however, their role in cells has been unclear. The aim of our work was to investigate the expression patterns of OCT4 isoforms in primary and metastatic CRC, providing us with useful information about their role in the development and progression of CRC.MethodsSurgical specimens from a total of 78 patients were collected and isolated from primary tumors (n = 47) and metastases (n = 31). The relative gene expression of OCT4 isoforms was investigated using the RT-qPCR method together with the TaqMan probes for particular OCT4 isoforms.ResultsOur results suggest significantly downregulated expression of the OCT4A and OCT4Bs isoforms in both primary (p = 0.0002 and p < 0.0001, respectively) and metastatic tumors (p = 0.0006 and p = 0.00051, respectively) when compared with the control samples. We also observed a correlation between reduced expression of all OCT4 isoforms and both primary and left-sided tumors (p = 0.001 and p = 0.030, respectively). On the other hand, the expression of all OCT4 isoforms was significantly upregulated in metastases compared with primary tumors (p < 0.0001).DiscussionUnlike previous reports, we found out that the expression of OCT4A, OCT4Bs, and all OCT4 isoforms was significantly reduced in primary tumors and metastases compared with control samples. On the other hand, we supposed that the expression rate of all OCT4 isoforms may be related to the cancer type and side, as well as to liver metastases. However, further studies are required to investigate the detailed expression patterns and significance of individual OCT4 isoforms in carcinogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Expression of OCT4 isoforms is reduced in primary colorectal cancer

Turyova,

Mikolajcik,

Grendar

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…Wang et al [ 20 ] claimed that the positive expression of Otc4A could be a warning sign for distant recurrence and poor prognosis of rectal cancer in patients undergoing chemoradiotherapy before surgery. Studies have shown that Otc4A protein overexpression plays a role in the development of CRC in the development of colon cancer, and Otc4A is a key transcription factor for maintaining the survival of colon cancer tumor transcription factor critical for the survival of stem cell-like cells [ 21 ]. NF- κ B falls into the category of a nuclear factor that binds to the gene regulatory region encoded by the immunoglobulin k light chain of activated B cells, and the abnormal activation of NF- κ B could enhance cancer cell proliferation by binding to the cyclin D1 promoter [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

The Transcription Factor Otc4A Stimulates the Proliferation, Invasion, and Stemness of Colorectal Cancer Cells by Inhibiting the Regulation of miR-7-5p on TLR4

Duan

Xie

et al. 2022

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Background. To investigate the effects and mechanism of octamer-binding transcription factor 4 (Otc4A) on proliferation, invasion, and stemness of colorectal cancer (CRC) cells. Methods. Firstly, normal fetal human cells (FHC, colon epithelial cells) and HT29 cells (CRC cells) were cultured. The expression levels of Otc4A, miR-7-5p, and TLR4 in cells were then detected by qRT-PCR. CCK-8 was adopted to measure cell proliferation rate after Otc4A, miR-7-5p, and TLR4, respectively, were either knocked out or overexpressed in HT29 cells. Later, the cell viability was detected by cell cloning assay; cell invasion by transwell; cell sphere-forming ability by sphere-formation assay; protein expression level of Otc4A, p65, p-p65, and TLR4 by western blot; and the targeting relationships between miR-7-5p and Otc4A as well as miR-7-5p and TLR4 by dual-luciferase reporter assay. Finally, chromatin immunoprecipitation was applied to verify the interaction between Otc4A and miR-7-5p. Results. In HT29 cells, Otc4A expression was significantly increased. Additionally, the knockdown of Otc4A prevented HT29 cells from proliferating, migrating, forming spheres, and activating NF–B signaling. Otc4A could negatively regulate miR-7-5p, and miR-7-5p could target TLR4 expression. Besides, a negative correlation was found between Otc4A and miR-7-5p. Finally, the knockdown of miR-7-5p or overexpression of TLR4 could significantly reverse the effect of the knockdown of Otc4A on HT29 cells. Conclusion. The transcription factor Otc4A can regulate the level of TLR4 by inhibiting the expression of miR-7-5p and then promote the proliferation and invasion of CRC cell HT29 as well as enhance cell stemness.

show abstract

“…OCT4 was reported to be remarkably high expressed in lung adenocarcinoma [19], colorectal cancer [20], cervical cancer [21], ovarian cancer [22], and so on. Our nding indicated that OCT4 could activate angiogenesis and promote ovarian cancer metastasis by regulating LRPPRC/ VEGFR2 axis.…”

Section: Discussionmentioning

confidence: 99%

OCT4 Promotes Ovarian Cancer Cell Metastasis and Angiogenesis via Modulating VEGFR2/LRPPRC Pathway

Xie

Wang

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Due to its high ability of metastasis, ovarian cancer remains the most lethal gynecological malignancy, yet its underlying mechanism remains unconfirmed. Objectives: The main purpose is to probe into the role and regulation mechanism of octamer-binding transcription factor 4 (OCT4) in angiogenesis and metastasis in ovarian cancer.Methods: Immunohistochemistry (IHC) and immunofluorescence in epithelial ovarian cancer specimens and benign ovarian tumor samples were performed, followed by RNA-sequencing and examination of angiogenesis, cell migration and invasion in OCT4 knockdown cell lines and the controls. Co-Immunoprecipitation (Co-IP), mass spectrometry, immunoblotting, immunofluorescence and chromatin immunoprecipitation (ChIP) analyses were conducted along with models of zebrafishes and nude mice of transplanted tumors to gain insights into the specific functions and mechanisms of action of OCT4 in ovarian cancer.Results: Firstly, we discovered that OCT4 expression was enhanced in ovarian cancer tissues significantly, especially in the metastatic lesions, indicating that OCT4 might be a key for the metastasis of ovarian cancer. Furtherly, we observed and verified that OCT4 promoted cell migration and invasion, and induced angiogenesis in vitro and in vivo. Mechanistically, OCT4 modulated the transcription of leucine‑rich PPR motif‑containing protein (LRPPRC)，and furtherly interacted with vascular endothelial growth factor receptor 2 (VEGFR2)/LRPPRC complex and ultimately triggered the downstream FAK/AKT signaling pathway . Conclusions: Together, through models of ovarian cancer cells, zebrafishes and tumor-transplanted mice, this study highlighted the importance of OCT4/LRPPRC/VEGFR2 signaling axis in metastasis of ovarian cancer and angiogenesis. Thus, our finding supplied a potential novel molecular-targeted approach for the treatment of ovarian cancer.

show abstract

Prognostic Value of Oct4 in Colorectal Cancer: Analysis Using Immunohistochemistry and Bioinformatics Validation

Cited by 7 publications

References 47 publications

Expression of OCT4 isoforms is reduced in primary colorectal cancer

Expression of OCT4 isoforms is reduced in primary colorectal cancer

The Transcription Factor Otc4A Stimulates the Proliferation, Invasion, and Stemness of Colorectal Cancer Cells by Inhibiting the Regulation of miR-7-5p on TLR4

OCT4 Promotes Ovarian Cancer Cell Metastasis and Angiogenesis via Modulating VEGFR2/LRPPRC Pathway

Contact Info

Product

Resources

About