[Corrigendum] FOXO3a‑mediated suppression of the self‑renewal capacity of sphere‑forming cells derived from the ovarian cancer SKOV3 cell line by 7‑difluoromethoxyl‑5,4’‑di‑n‑octyl genistein

Epithelial ovarian cancer has the highest mortality rate of all gynecologic cancers. Cancer stem cells are considered to be the initiating cells of tumors. It is known that spheroid culture promotes ovarian cancer cells to acquire stem cell characteristics and to become stem cell-like. But the mechanisms remain largely unclear. Our data show that autophagy is sustainably activated in ovarian cancer spheroid cells. Inhibition of autophagy by knockdown of ATG5 abolishes the self-renewal ability of ovarian cancer spheroid cells. Knockdown of ATG5 prevents ovarian cancer spheroid cells to enter quiescent state. Autophagy is critical for quiescent ovarian cancer spheroid cells to reenter the cell cycle because rapamycin can promote quiescent ovarian cancer spheroid cells to form colonies on soft agar and knockdown of ATG5 can arrest ovarian cancer cells in G0/G1. Autophagy and NRF2 form a positive feedback regulation loop to regulate reactive oxygen species (ROS) levels in ovarian cancer spheroid cells. The optimal ROS level, neither too high nor too low, facilitates the self-renewal marker, NOTCH1, to reach to the highest level. Bafilomycin A1 can impair the self-renewal of ovarian cancer spheroid cells by disturbing ROS levels.

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miR-29c-3p regulates proliferation and migration in ovarian cancer by targeting KIF4A

World Journal of Surgical Oncology ◽

10.1186/s12957-020-02088-z ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Songwei Feng ◽

Shanhui Luo ◽

Chenchen Ji ◽

Jia Shi

Keyword(s):

Ovarian Cancer ◽

Cell Line ◽

Cancer Prognosis ◽

Expression Level ◽

Luciferase Reporter ◽

Epithelial Cell Line ◽

Skov3 Cell ◽

Ovarian Carcinoma Cell Line ◽

And Migration ◽

Proliferation And Migration

Abstract Background Increasing evidence suggested that microRNA and kinesin superfamily proteins play an essential role in ovarian cancer. The association between KIF4A and ovarian cancer (OC) was investigated in this study. Methods We performed bioinformatics analysis in the GEO database to screen out the differentially expressed miRNAs (DEmiRNAs) associated with ovarian cancer prognosis. Upstream targeting prediction for KIF4A was acquired by using the mirDIP database. The potential regulatory factor miR-29c-3p for KIF4A was obtained from the intersection of the above all miRNAs. The prognosis of KIF4A and target-miRNA in OC was obtained in the subsequent analysis. qRT-PCR and Western blot detected KIF4A expression level in IOSE80 (human normal ovarian epithelial cell line). In the meantime, the gene expression level was detected in A2780, HO-8910PM, COC1, and SKOV3 cell lines (human ovarian carcinoma cell line). MTT and colony formation assays were used to detect cell proliferation of SKOV3 cell line. The following assays detected cell migration through the use of transwell and wound heal assays. Targeted binding relationship between KIF4A and miRNA was detected by using the dual-luciferase reporter assay. Results Both high expression of KIF4A and lower expression of miR-29c-3p could be used as biomarkers indicating poor prognosis in OC patients. Cellular function tests confirmed that when KIF4A was silenced, it inhibited the proliferation and migration of OC cells. In addition, 3′-UTR of KIF4A had a direct binding site with miR-29c-3p, which indicated that the expression of KIF4A could be regulated by miR-29c-3p. In subsequent assays, the proliferation and migration of OC cells were inhibited by the overexpression of miR-29c-3p. At the same time, rescue experiments also confirmed that the promotion of KIF4A could be reversed by miR-29c-3p. Conclusion In a word, our data revealed a new mechanism for the role of KIF4A in the occurrence and development of OC.

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Intratumoral Heterogeneity in the Self-Renewal and Tumorigenic Differentiation of Ovarian Cancer

Stem Cells ◽

10.1002/stem.1029 ◽

2012 ◽

Vol 30 (3) ◽

pp. 415-424 ◽

Cited By ~ 28

Author(s):

Sagi Abelson ◽

Yeela Shamai ◽

Liron Berger ◽

Roni Shouval ◽

Karl Skorecki ◽

...

Keyword(s):

Ovarian Cancer ◽

Intratumoral Heterogeneity ◽

The Self ◽

Self Renewal

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Forkhead Box Protein C2 Promotes Epithelial-Mesenchymal Transition, Migration and Invasion in Cisplatin-Resistant Human Ovarian Cancer Cell Line (SKOV3/CDDP)

Cellular Physiology and Biochemistry ◽

10.1159/000447818 ◽

2016 ◽

Vol 39 (3) ◽

pp. 1098-1110 ◽

Cited By ~ 11

Author(s):

Chanjuan Li ◽

Hongjuan Ding ◽

Jing Tian ◽

Lili Wu ◽

Yun Wang ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Cell Line ◽

Epithelial Mesenchymal Transition ◽

Ovarian Cancer Cell Line ◽

Cancer Cell Line ◽

Ovarian Cancer Cells ◽

Skov3 Cell ◽

Mesenchymal Transition ◽

Forkhead Box

Background/Aims: Forkhead Box Protein C2 (FOXC2) has been reported to be overexpressed in a variety of human cancers. However, it is unclear whether FOXC2 regulates epithelial-mesenchymal transition (EMT) in CDDP-resistant ovarian cancer cells. The aim of this study is to investigate the effects of FOXC2 on EMT and invasive characteristics of CDDP-resistant ovarian cancer cells and the underlying molecular mechanism. Methods: MTT, Western blot, scratch wound healing, matrigel transwell invasion, attachment and detachment assays were performed to detect half maximal inhibitory concentration (IC50) of CDDP, expression of EMT-related proteins and invasive characteristics in CDDP-resistant ovarian cancer cell line (SKOV3/CDDP) and its parental cell line (SKOV3). Small hairpin RNA (shRNA) was used to knockdown FOXC2 and analyze the effect of FOXC2 knockdown on EMT and invasive characteristics of SKOV3/CDDP cells. Also, the effect of FOXC2 upregulation on EMT and invasive characteristics of SKOV3 cells was analyzed. Furthermore, the molecular mechanism underlying FOXC2-regulating EMT in ovarian cancer cells was determined. Results: Compared with parental SKOV3 cell line, SKOV3/CDDP showed higher IC50 of CDDP (43.26μM) (P<0.01) and acquired EMT phenotype and invasive characteristics. Gain- and loss-of-function assays indicated that shRNA-mediated FOXC2 knockdown could reverse EMT and reduce the capacity of migration, invasion, attachment and detachment in SKOV3/CDDP cell line and upregulation of FOXC2 could induce the reverse effects in parental SKOV3 cell line. Furthermore, it was found that activation of ERK or AKT/GSK-3β signaling pathways was involved in FOXC2-promoting EMT in CDDP-resistant ovarian cancer cells. Conclusions: Taken together, these data demonstrate that FOXC2 may be a promoter of EMT phenotype in CDDP-resistant ovarian cancer cells and a potential therapeutic target for the treatment of advanced ovarian cancer.

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Abstract 2495: hPaf1/PD2 interacts with OCT3/4 in maintenance of the self-renewal process of ovarian cancer stem cells

10.1158/1538-7445.am2016-2495 ◽

2016 ◽

Author(s):

Saswati Karmakar ◽

Parthasarathy Seshacharyulu ◽

Arokia Priyanka Vaz ◽

Imayavaramban Lakshmanan ◽

Moorthy Palanimuthu Ponnusamy ◽

...

Keyword(s):

Ovarian Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Renewal Process ◽

The Self ◽

Ovarian Cancer Stem Cells ◽

Self Renewal

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Crucial role of HMGA1 in the self-renewal and drug resistance of ovarian cancer stem cells

Experimental & Molecular Medicine ◽

10.1038/emm.2016.73 ◽

2016 ◽

Vol 48 (8) ◽

pp. e255-e255 ◽

Cited By ~ 21

Author(s):

Dae Kyoung Kim ◽

Eun Jin Seo ◽

Eun J Choi ◽

Su In Lee ◽

Yang Woo Kwon ◽

...

Keyword(s):

Ovarian Cancer ◽

Stem Cells ◽

Drug Resistance ◽

Cancer Stem Cells ◽

Crucial Role ◽

The Self ◽

Ovarian Cancer Stem Cells ◽

Self Renewal

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Sec23a Inhibits The Self-Renewal of Melanoma Cancer Stem Cells via Inactivation of ER-Phagy

10.21203/rs.3.rs-579892/v1 ◽

2021 ◽

Author(s):

H.Rosie Xing ◽

Zhiwei Sun ◽

Doudou Liu ◽

Bin Zeng ◽

Qiting Zhao ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Er Stress ◽

Cell Line ◽

Melanoma Cell ◽

Melanoma Cell Line ◽

Human Melanoma ◽

The Self ◽

Human Melanoma Cell ◽

Self Renewal

Abstract Background The genesis and developments of solid tumors, analogous to the renewal of healthy tissues, are driven by a subpopulation of dedicated stem cells, known as cancer stem cells (CSCs), that exhibit long-tern clonal repopulation and self-renewal capacity. CSCs may regulate tumor initiation, growth, dormancy, metastasis, recurrence and chemoresistance. While autophagy has been proposed as a regulator of the stemness of CSCs, the underlying mechanisms requires further elucidation. Methods The subpopulation of CSCs in human melanoma cell line M14 was established by repetitive enrichments for cells that consistently display anchorage-independent spheroid growth. The stemness properties of the CSCs were confirmed in vitro by the expressions of stemness marker genes, the single-cell cloning assay and the serial spheroid formation assay. Subcutaneous tumor transplantation assay in BALB/c nude mice was performed to test the stemness properties of the CSCs in vivo. The autophagic activity in cells was confirmed by the protein level of LC3 and P62, mRFP-LC3B punta and cytoplasmic accumulation of autolysosomes. The morphology of ER was detected with transmission electron microscopy. Results In the present study, by employing a stable CSC cell line derived from human melanoma cell line M14, we show for the first time that Sec23a inhibits the self-renewal of melanoma CSCs via inactivation of ER-phagy. Mechanistically, inhibition of Sec23a reduces ER stress and consequently FAM134B-induced ER-phagy. Furthermore, TCGA data mining and analysis show that Sec23a is a favorable diagnostic and prognostic marker for human skin cutaneous melanoma (SKCM). Conclusion Herein, this study has elucidated a new mechanism underlying the regulation of autophagy on stemness, i.e. CSCs can exploit the SEC23A/ER-stress/FAM134B/ER-phagy axis for the self-renewal. The results provide new ideas for comprehensive exploration of the regulatory network of CSC self-renewal and new potential targets for CSCs-based therapy strategies for malignant tumors.

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