Impact of modulation of telomerase and cancer stem‐cell marker OCT4 axis in cervical cancer pathogenesis with underlying HPV16 infection

Tiwari, Diptika; Das, Chandana; Sultana, Rizwana; Kakoti, Shantipriya; Khan, Mateen A.; Dongre, Anita; Husain, Syed Akhtar; Bose, Purabi Deka; Bose, Sujoy

doi:10.1002/jcb.29501

Cited by 6 publications

(6 citation statements)

References 49 publications

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“…Tyagi et al (43) clarified the role of the HPV E6 oncogene in the maintenance of the stemness characteristics (stemness markers OCT4, SOX2, Nanog, Lrig1, and CD133) of CSCs in CC. Significant OCT4 marker upregulation has also been found in CC, which has an association with disease susceptibility and severity (44). Other research has indicated that ALDH1 and POU class 5 homeobox 1 (OCT4) may be utilized as biomarkers for the early detection of CC or monitoring the treatment of patients (45).…”

Section: Discussionmentioning

confidence: 99%

miR-326 inhibits the cell proliferation and cancer stem cell-like property of cervical cancer in vitro and oncogenesis in vivo via targeting TCF4

Zhang¹,

He²,

Wang³

et al. 2020

Ann Transl Med

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Background: Cervical cancer ranks as one of the most prevalent female malignancies globally, and its treatment with new targets has been the focus of current research. The present study set out to investigate the function of microRNA-326 (miR-326) in vitro and in vivo and to verify the direct targeting of transcription factor 4 (TCF4) by miR-326. Methods: The detection of messenger RNA (mRNA) expressing miR-326 and TCF4 in cervical cancer cell lines and tumor samples was conducted using quantitative real-time polymerase chain (qRT-PCR). A dualluciferase reporter assay was carried out to detect the target relationship of miR-326 with TCF4. A Cell Counting Kit-8 (CCK-8) assay was employed to detect the effect of miR-326 on CasKi cell viability. Flow cytometry and western blotting were employed to examine the effects of miR-326 on cancer stem cell (CSC)like property. Tumor weight was measured in orthotopic xenograft mouse models. Immunohistochemistry was employed to analyze the protein expression levels of Ki-67, proliferating cell nuclear antigen (PCNA), CD44, and SRY-box 4 (SOX4). Result: Downregulation of the mRNA expression levels of miR-326 was observed in cervical cancer cell lines and tumor tissue, while the levels of TCF4 were upregulated. The dual-luciferase reporter assay revealed binding of miR-326 to the three prime untranslated region (3'-UTR) of TCF4. In vitro assays demonstrated that miR-326 inhibited CasKi cell proliferation through regulating TCF4. miR-326 also suppressed the CSC-like property of CasKi cells by targeting TCF4. Furthermore, the protein expression levels of cyclin D1, β-catenin, and c-Myc were decreased when miR-326 was added to TCF4-transfected cells. In vivo assays demonstrated that miR-326 inhibited tumor weight, growth, and the protein expression levels of Ki-67, PCNA, CD44, SOX4, and β-catenin.Conclusions: miR-326 acted in a tumor-suppressive manner through its regulation of TCF4, and has potential as a biomarker or therapeutic target for cervical cancer.

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Section: Discussionmentioning

confidence: 99%

miR-326 inhibits the cell proliferation and cancer stem cell-like property of cervical cancer in vitro and oncogenesis in vivo via targeting TCF4

Zhang¹,

He²,

Wang³

et al. 2020

Ann Transl Med

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“…However, different studies indicated that OCT4 expression in tumor tissues is enhanced in different cancers . 9,30 In the study conducted by Talebi et al, OCT4 expression was analyzed in normal and colon adenocarcinoma tissues. Their results showed no statistically significant association between OCT4 expression and cancer incidence .…”

Section: Association Between Oct4 Expression Nanog Expression and The Patients' Clinical And Pathological Characteristicsmentioning

confidence: 99%

Expression patterns and clinical significance of the potential cancer stem cell markers OCT4 and NANOG in colorectal cancer patients

Roudi

Barodabi

Madjd

et al. 2020

Molecular & Cellular Oncology

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Colorectal cancer (CRC) is one of the most important malignancies and causes of cancer-related deaths worldwide. Cancer stem cell markers identification could be helpful to acquire important prognostic information and develop new treatment regimens. This study aimed to evaluate the expression of OCT4 and NANOG in CRC patients and their clinical significance.Totally 359 CRC samples were stained for OCT4 and NANOG expression using tissue microarray. The correlation between their expression and clinical and pathological features was explored.The majority of CRC cases showed low-level expression of OCT4 (80%) and NANOG (75%). Lower expression of OCT4 was more often detected in CRC cases with no vascular involvement (P = .01). Also, a trend found between low level of OCT4 expression and absence of distant metastasis or lymph node involvement (P = .07 and P = .09, respectively). Surprisingly, a significant positive correlation was observed between NANOG expression and cellular differentiation (P = .05). Our combined analysis demonstrated that OCT4 low /NANOG low phenotype has frequently seen in colorectal cancer cases with no vascular invasion (P = .05).Our observations indicated that higher expression of OCT4 and NANOG can confer malignant and aggressive behavior to CRC. Evaluation of the co-expression of these cancer stem cell markers can serve a new diagnostic and prognostic approach in CRC patients. These findings also suggested that simultaneous expression of OCT4 and NANOG can be considered as a therapeutic marker for targeted therapy of CRC, especially in advanced stages.

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“…For instance, OCT4 collaborated with NCOR1 precipitated transcriptional repression on high expression genes in MEFs ( 22 ). Additionally, previous studies suggested that HPV16 E6 upregulated OCT4 expression by targeting HDAC1 for proteasomal degradation ( 17 , 28 b). Moreover, JNK-phosphorylated OCT4 reduced OCT4 protein stability which was enhanced by KAP1 overexpression ( 29 , 30 ).…”

Section: Discussionmentioning

confidence: 94%

“…The transcription factor OCT4 takes a crucial role in maintaining self-renewal and pluripotency of embryonic stem cells ( 16 ). The OCT4 was related to cervical cancer susceptiveness, which colocalized in the nucleus with HPV16 E6, suggesting the potential role of viral HPV16 E6 in stem-like cancer cells through regulating OCT4 expression ( 17 a). However, whether HPV16 E6-induced OCT4 expression could influence the level of p53 is still unknown.…”

Section: Introductionmentioning

confidence: 99%

HPV16 E6-Activated OCT4 Promotes Cervical Cancer Progression by Suppressing p53 Expression via Co-Repressor NCOR1

Shu

Liu

et al. 2022

Front. Oncol.

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Human papillomaviruses (HPV), mainly HPV16 and HPV18, of high-risk classification are involved in cervical cancer carcinogenesis and progression. Octamer-binding transcription factor 4 (OCT4) is a key transcription factor that is increased in various cancer types. Cervical cancer patients with higher levels of OCT4 had worse survival rates. However, the definite mechanisms underlying its function in the development of cervical cancer still remain to be explicated. Here, our study demonstrated that OCT4 expression was slightly increased in cervical cancer tissues than in precancerous ones. However, OCT4 was significantly upregulated in HPV16-positive tissues, in contrast to the expression profiling for p53. Moreover, knockdown of HPV16 E6 in SiHa cells suppressed the expression of OCT4 with impaired activities of cell proliferation, migration, and invasion, while it recovered the expression of p53. Overexpression of OCT4 and p53 exerted opposite roles on cell proliferation, migration, invasion, and colony formation of cervical cancer cells. More importantly, the enforced expression of OCT4 augmented p53-inhibited cell migration, invasion, and colony formation in human cervical cancer by promoting EMT. Finally, we identified that OCT4 could bind to the p53 promoter region to repress p53 expression by recruiting co-repressor NCOR1 using luciferase, ChIP, and co-IP experiments. We further illustrated that OCT4 not only increased the lung metastasis of cervical cancer but also effectively reversed p53-inhibited lung metastasis. In conclusion, our results suggested that HPV16 E6 activated the expression of OCT4 and subsequently crippled the transcription of p53 via co-repressor NCOR1, which contributed to cervical cancer progression.

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Impact of modulation of telomerase and cancer stem‐cell marker OCT4 axis in cervical cancer pathogenesis with underlying HPV16 infection

Cited by 6 publications

References 49 publications

miR-326 inhibits the cell proliferation and cancer stem cell-like property of cervical cancer in vitro and oncogenesis in vivo via targeting TCF4

miR-326 inhibits the cell proliferation and cancer stem cell-like property of cervical cancer in vitro and oncogenesis in vivo via targeting TCF4

Expression patterns and clinical significance of the potential cancer stem cell markers OCT4 and NANOG in colorectal cancer patients

HPV16 E6-Activated OCT4 Promotes Cervical Cancer Progression by Suppressing p53 Expression via Co-Repressor NCOR1

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