c-Rel Promotes Invasion of Choriocarcinoma Cells via PI3K/AKT Signaling

Sekiya, Yoko; Yamamoto, Eiko; Niimi, Keiko; Nishino, Kimihiro; Nakamura, Kenichi; Kotani, Tomomi; Kajiyama, Hiroaki; Shibata, Kiyosumi; Kikkawa, Fumitaka

doi:10.1159/000458529

Cited by 15 publications

(10 citation statements)

References 28 publications

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“…In addition, GTD is also been characterized by abnormal proliferation and apoptosis 13,14 and associated with signal pathway regulation. Sekiya found that c‐Rel might play a role in promoting the invasion of choriocarcinoma cells through PI3K/AKT signalling 15 . miR‐30a‐5p which we studied in this article may play an important role in the regulation of ERK signalling 16 …”

Section: Introductionmentioning

confidence: 85%

MiR‐30a‐5p inhibits proliferation and metastasis of hydatidiform mole by regulating B3GNT5 through ERK/AKT pathways

Guo

Sun

Liao

et al. 2020

J Cellular Molecular Medi

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Hydatidiform moles are gestational trophoblastic disease. They are abnormal proliferations of trophoblast cells that have the potential to become cancerous. miR‐miR30a‐5p is a tumour suppressor that participates in the development of numerous diseases. However, the role of miR‐30a in hydatidiform moles and the mechanisms underlying its effects are presently unclear. This study explored the levels of miR‐30a and B3GNT5 expression in human hydatidiform mole tissue. The results showed that miR‐30a and B3GNT5 were differentially expressed in normal placenta and hydatidiform mole, and miR‐30a decreased cell proliferation, invasion and migration in trophoblast cell lines. Upon further examination, it was confirmed that miR‐30a directly targeted the 3’untranslated region of B3GNT5 using a dual‐luciferase assay. The results of the present study also revealed that miR‐30a reduced the proliferation, invasion and migration ability in JAR and BeWo cells by regulating B3GNT5, which may inactivate the ERK and AKT signalling pathways. This study demonstrated that miR‐30a was a novel target B3GNT5 that serves an important role in the development of hydatidiform moles, suggesting that miR‐30a may serve as a novel potential biomarker or useful diagnostic and therapeutic tool for hydatidiform moles in clinical settings.

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Section: Introductionmentioning

confidence: 85%

MiR‐30a‐5p inhibits proliferation and metastasis of hydatidiform mole by regulating B3GNT5 through ERK/AKT pathways

Guo

Sun

Liao

et al. 2020

J Cellular Molecular Medi

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“…The activation of PI3K/AKT signaling pathway had been verified in numerous cancers, including choriocarcinoma, which was involved in the modulation of cell survival, proliferation, differentiation, and migration. 27,28 5-Fu can inactivate PI3K/AKT signaling pathway in many cancer cells. 29 Zhang et al 30 proved that downregulation of USP22 potentiated the chemosensitivity of hepatocellular carcinoma cells to 5-Fu by inactivating AKT.…”

Section: Discussionmentioning

confidence: 99%

Lidocine potentiates the cytotoxicity of 5‐fluorouracil to choriocarcinoma cells by downregulating ABC transport proteins expression

Zhang

Pang

et al. 2019

J of Cellular Biochemistry

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Choriocarcinoma is a gestational trophoblastic cancer, which often occurs in the first 3 months of pregnancy. 5‐Fluorouracil (5‐Fu) is the widely used chemotherapeutic drug for choriocarcinoma but limited by drug resistance. Lidocaine, an aminamide‐type anesthetic, shows potential anticancer and chemosensitization effects in recent years. Herein, we tested the possible chemosensitization activity of lidocaine on the cytotoxicity of 5‐Fu in choriocarcinoma cells. Viabilities and apoptosis of choriocarcinoma JEG‐3 and JAR cells after lidocaine and/or 5‐Fu treatment were detected using Cell Counting Kit‐8 assay, annexin V‐FITC/PI (fluorescein isothiocyanate/propidium iodide) staining and Western blot analysis, respectively. Quantitative reverse transcription polymerase chain reaction was done to measure breast cancer resistance protein (ABCG2) messenger RNA level. Western blot analysis was carried out to detect ABCG2, P‐glycoprotein (P‐gp), MRP1, and MRP2 protein levels. pEX‐ABCG2 was transfected to elevate ABCG2 level. Then, the influence of ABCG2 on lidocaine + 5‐Fu‐caused cell viability loss, apoptosis, and inactivation of PI3K/AKT pathway were analyzed. We found that lidocaine in low concentration had no significant cytotoxicity to JEG‐3 and JAR cells, but stimulated cell apoptosis in high concentration. Moreover, lidocaine potentiated the cytotoxicity of 5‐Fu to JEG‐3 and JAR cells through decreasing viability and increasing apoptosis. Lidocaine treatment reduced the ABCG2, P‐gp, MRP1, and MRP2 protein levels in cells. Overexpression of ABCG2 reversed the synergistic effects of lidocaine + 5‐Fu on JEG‐3 and JAR cell viability and apoptosis, as well as PI3K/AKT pathway. Our research verified that lidocaine potentiated the cytotoxicity of 5‐Fu to choriocarcinoma cells by downregulating ATP‐binding cassette (ABC) transport proteins expression.

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“…NF-κB subunit c-Rel plays an important role in initiation of inflammatory responses, but also functions as a transcriptional repressor of inflammatory genes [45]. NF-κB subunit c-Rel expresses in villi of normal placenta, and plays a key role in enhancing the invasion of choriocarcinoma cells through phosphatidylinositol-3-OH kinase-Akt signaling [46]. Low levels of NF-κB subunits c-Rel, p50, and p105 in myometrium are favorable for pregnancy maintenance, but increasing expression of p65, c-Rel, and p50 subunits is associated with the onset of parturition in humans [29].…”

Section: Discussionmentioning

confidence: 99%

Expression of nuclear factor kappa B in ovine maternal inguinal lymph nodes during early pregnancy

Zhang

Yang

et al. 2022

BMC Vet Res

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Background Pregnancy-induced immunological changes contribute to the maternal immune tolerance. Nuclear factor kappa B (NF-κB) pathway participates in regulating both innate and adaptive immunities, and lymph nodes play key roles in adaptive immune reaction. However, it is unclear whether early pregnancy changes the expression of NF-κB family in maternal lymph node in sheep. Methods In this study, the samples of inguinal lymph nodes were collected from ewes on day 16 of the estrous cycle, and on days 13, 16 and 25 of pregnancy, and expression of NF-κB family, including NF-κB p105 (NFKB1), NF-κB p100 (NFKB2), p65 (RELA), RelB (RELB) and c-Rel (REL), were analyzed through real-time quantitative PCR, Western blot and immunohistochemical analysis. Results The expression levels of NF-κB p105 and c-Rel downregulated, but NF-κB p100 upregulated on day 25 of pregnancy. The expression levels of p65, RelB and c-Rel peaked at day 13 of pregnancy, and expression level of RelB was higher during early pregnancy comparing to day 16 of the estrous cycle. In addition, p65 protein was located in the subcapsular sinus and lymph sinuses. Conclusion This paper reported for the first time that early pregnancy has effects on the expression of NF-κB family, which may contribute to the maternal immunoregulation through blood circulation and lymph circulation during early pregnancy in sheep.

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c-Rel Promotes Invasion of Choriocarcinoma Cells via PI3K/AKT Signaling

Cited by 15 publications

References 28 publications

MiR‐30a‐5p inhibits proliferation and metastasis of hydatidiform mole by regulating B3GNT5 through ERK/AKT pathways

MiR‐30a‐5p inhibits proliferation and metastasis of hydatidiform mole by regulating B3GNT5 through ERK/AKT pathways

Lidocine potentiates the cytotoxicity of 5‐fluorouracil to choriocarcinoma cells by downregulating ABC transport proteins expression

Expression of nuclear factor kappa B in ovine maternal inguinal lymph nodes during early pregnancy

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