Increased expression of stemness genes Rex-1, Oct-4, Nanog, and Sox-2 in women with ovarian endometriosis versus normal endometrium: A case-control study

Shariati, Fatameh; Favaedi, Raha; Ramazanali, Fariba; Ghoraeian, Pegah; Afsharian, Parvaneh; Aflatoonian, Behrouz; Aflatoonian, Reza; Shahhoseini, Maryam

doi:10.18502/ijrm.v16i12.3684

Cited by 18 publications

(13 citation statements)

References 25 publications

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“…Moreover, NNK increases the expression levels of OCT-4, SOX-2, and Nanog, which are thought to play an important role in tumour stem cells. It is consistent with previous research that elevated levels may indicate increased stemness in tumour cells [23][24][25] . Our experiments also con rmed that NNK can promote gemcitabine resistance.…”

Section: Discussionsupporting

confidence: 93%

The Tobacco Metabolite NNK Enhances Pancreatic Cancer Cell Stemness and Chemoresistance by Activating the β2AR-Akt Autophagy Axis

Chen

Zhang

Liu

et al. 2021

Preprint

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Background: Low responsiveness to chemotherapy is an important cause of poor prognosis in pancreatic cancer. Smoking is a high-risk factor for pancreatic cancer and its resistance to gemcitabine; however, the underlying mechanisms remain unclear. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the main metabolite of tobacco burning and has been shown to be associated with cancer development and chemoresistance, but in pancreatic cancer, its mechanism remains poorly understood.Methods: The effect of NNK on pancreatic cancer cell viability was confirmed by using Cell Counting Kit-8 and colony formation assays. Stem cell sphere formation assays and western blotting/qPCR measurements of stemness-related molecules were used to detect pancreatic cancer cell stemness. The pancreatic cancer autophagy status was evaluated by immunofluorescence staining of LC3 and western blotting/qPCR analysis of autophagy-related molecules.Results: NNK promoted stemness and gemcitabine resistance in pancreatic cancer cell lines. Furthermore, NNK intervention increased autophagy and changed the expression levels of autophagy-related markers, which preliminarily confirmed the activation of autophagy by NNK. Finally, the results showed that NNK-promoted stemness, and gemcitabine resistance was activated by the autophagy pathway, which was mediated by the β2AR-Akt signalling pathway.Conclusions: Autophagy induced by activating the NNK-induced β2AR-Akt signalling pathway promoted stemness and gemcitabine resistance in pancreatic cancer cells.

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Section: Discussionsupporting

confidence: 93%

The Tobacco Metabolite NNK Enhances Pancreatic Cancer Cell Stemness and Chemoresistance by Activating the β2AR-Akt Autophagy Axis

Chen

Zhang

Liu

et al. 2021

Preprint

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“…In 2016, Proestling et al reported that endometriotic tissues have abnormal expression of SOX2, NANOG, and OCT4, in which OCT4 could stimulate endometrial cell migration [19]. We have also observed changes in the expression level of stemness genes which show contradictory results overall [18,19].…”

Section: Enhanced Stemness Gene Expression In E-menscsmentioning

confidence: 67%

“…Also, the stemness and pluripotency-related genes play an important role in the pathogenesis of endometriosis [15]. Several research studies have reported that the expression of stemness genes such as OCT-4 and SOX-2 was increased in patients with endometriosis [15,18,19]. It seems that increased expression of these genes may contributes to the development and spread of endometriosis [15].…”

Section: Introductionmentioning

confidence: 99%

A Comparative Study of Gene Expression in Menstrual Blood-Derived Stromal Cells between Endometriosis and Healthy Women

Sahraei

Asl

Kalhor

et al. 2022

BioMed Research International

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Background. Research into the pathogenesis of endometriosis would substantially promote its effective treatment and early diagnosis. Currently, accumulating evidence has shed light on the importance of endometrial stem cells within the menstrual blood which are involved in the establishment and progression of endometriotic lesions in a retrograde manner. Objectives. We aimed to identify the differences in some genes’ expression between menstrual blood-derived mesenchymal stem cells (MenSCs) isolated from endometriosis patients (E-MenSCs) and MenSCs from healthy women (NE-MenSCs). Methods. Menstrual blood samples (2-3 mL) from healthy and endometriosis women in the age range of 22–35 years were collected. Isolated MenSCs by the Ficoll-Paque density-gradient centrifugation method were characterized by flow cytometry. MenSCs were evaluated for key related endometriosis genes by real-time-PCR. Results. E-MenSCs were morphologically different from NE-MenSCs and showed, respectively, higher and lower expression of CD10 and CD9. Furthermore, E-MenSCs had higher expression of Cyclin D1 (a cell cycle-related gene) and MMP-2 and MMP-9 (migration- and invasion-related genes) genes compared with NE-MenSCs. Despite higher cell proliferation in E-MenSCs, the BAX/BCL-2 ratio was significantly lower in E-MenSCs compared to NE-MenSCs. Also, the level of inflammatory genes such as IL1β, IL6, IL8, and NF-κB and stemness genes including SOX2 and SALL4 was increased in E-MenSCs compared with NE-MenSCs. Further, VEGF, as a potent angiogenic factor, showed a significant increase in E-MenSCs rather than NE-MenSCs. However, NE-MenSCs showed increased ER-α and β-catenin when compared with E-MenSCs. Conclusion. Here, we showed that there are gene expression differences between E-MenSCs and NE-MenSCs. These findings propose that MenSCs could play key role in the pathogenesis of endometriosis and further support the menstrual blood retrograde theory of endometriosis formation. This could be of great importance in exploiting promising therapeutic targets and new biomarkers for endometriosis treatment and prognosis.

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“…An undifferentiated HGC-27 cell line was used in the present study and it was found that KLK6 silencing reduced the proportion of the cell population expressing CD44 and CD133, which are markers of tumor cell stemness (6). SOX2, Oct-4 and Nanog, which are involved in the process of tumorigenesis, invasion, metastasis and recurrence (41), are key regulators of tumor cell self-renewal, proliferation and differentiation, and also act as predictive biomarkers of poor prognosis for ovarian endometriosis (42), esophagus cancer (43) and etc. In the present study, it was found that KLK6 silencing, in turn, inhibited the protein expression level of the tumor cell stemness maintenance factors, SOX2, Oct-4 and Nanog, suggesting that KLK6 may suppress gastric cancer cell growth by inhibiting the stem-like properties and behaviors.…”

Section: Discussionmentioning

confidence: 99%

KLK6 mediates stemness and metabolism of gastric carcinoma cells via the PI3K/AKT/mTOR signaling pathway

Zhou

et al. 2021

Oncol Lett

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Gastric cancer is a common tumor of the digestive system, which can occur in any part of the stomach. Kallikrein 6 (KLK6) is a trypsin-like serine protease and has been found to be involved in extracellular matrix remodeling, tumor invasion and nervous system plasticity. Our previous study reported that KLK6 suppressed HGC-27 gastric cancer cell growth by inhibiting epithelial-mesenchymal transition; however, the mechanism of action underlying the effect of KLK6 still remains unclear. The aim of the present study was to investigate the effect and the underlying mechanism of KLK6 on stem cell-like properties and metabolism in gastric carcinoma cells. The HGC-27 cell line was transfected with KLK6 overexpression (OV-KLK6) and interference (short hairpin-KLK6) vectors, then the transfection efficiency was confirmed using western blot analysis and reverse transcription-quantitative PCR. The percentage of CD133 + and CD44 + cells was detected using flow cytometry, while the protein expression levels of the stem-associated genes, Nanog, Oct-4, SOX2 and Notch1, the metabolic markers, hexokinase (HK)1, HK2, GLUT1, and the proteins within the PI3K signaling pathway, phosphorylated (p)-PI3K, p-AKT and p-mTOR, were determined using western blot analysis. Biochemical kits were used to measure ATP production, lactic acid content and glucose uptake. A tumorigenicity assay was performed with nude mice to detect gastric tumor volume, and the protein expression level of Oct-4, Nanog, HK1, HK2 and GLUT1, and the mRNA expression level of KLK6 was also determined in gastric tumor tissues of mice. Compared with that in the control group, KLK6 protein and mRNA expression levels were significantly decreased in the four sh-RNA groups (P<0.05). Among them, sh-RNA-3 induced the lowest KLK6 expression and was used to silence KLK6 in subsequent experiments. Compared with that in the control and negative control groups, the percentage of CD133 + and CD44 + cells, the protein expression level of Oct-4, Nanog, HK1, HK2, GLUT1, p-PI3K, p-AKT and p-mTOR, and ATP content, lactic acid production, glucose uptake and gastric tumor volume were significantly decreased by sh-KLK6 (P<0.05), whereas KLK6 overexpression induced the opposite effect (P<0.05). In conclusion, KLK6 modulated stemness properties and cell metabolic profile in gastric carcinoma cells and the mechanism may be associated with the PI3K/AKT/mTOR signaling pathway.

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Increased expression of stemness genes Rex-1, Oct-4, Nanog, and Sox-2 in women with ovarian endometriosis versus normal endometrium: A case-control study

Abstract: .

Cited by 18 publications

References 25 publications

The Tobacco Metabolite NNK Enhances Pancreatic Cancer Cell Stemness and Chemoresistance by Activating the β2AR-Akt Autophagy Axis

The Tobacco Metabolite NNK Enhances Pancreatic Cancer Cell Stemness and Chemoresistance by Activating the β2AR-Akt Autophagy Axis

A Comparative Study of Gene Expression in Menstrual Blood-Derived Stromal Cells between Endometriosis and Healthy Women

KLK6 mediates stemness and metabolism of gastric carcinoma cells via the PI3K/AKT/mTOR signaling pathway

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