GINS2 affects cell viability, cell apoptosis, and cell cycle progression of pancreatic cancer cells via MAPK/ERK pathway

Zhang, Miao; He, Saifei; Ma, Xing; Ye, Ying; Wang, Guoyu; Zhuang, Juhua; Song, Yanan; Xia, Weiya

doi:10.7150/jca.38386

Cited by 17 publications

(18 citation statements)

References 33 publications

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“…Overexpression of UBE2T and PTTG1 promotes HCC cell growth, migration and invasion through activating Akt pathway [69,70]. GINS2 is a member of the GINS complex and participates in DNA replication and cell cycle regulation in most tumors, such as pancreatic cancer [41], bladder cancer [71], and lung cancer [72]. Bioinformatic analysis showed that both individual GINS2 and the whole GINS complex could be prognostic biomarkers for HCC [73].…”

Section: Discussionmentioning

confidence: 99%

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Oleate acid-stimulated HMMR expression by CEBPα is associated with nonalcoholic steatohepatitis and hepatocellular carcinoma

Zhang¹,

Liu²,

Xie³

et al. 2020

Int. J. Biol. Sci.

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Non-alcoholic steatohepatitis (NASH) is a type of nonalcoholic fatty liver disease and has become a major risk factor for hepatocellular carcinoma (HCC). However, the underlying pathophysiological mechanisms are still elusive. Here, we identify hyaluronan-mediated motility receptor (HMMR) as a critical gene associated with NASH/HCC by combination of bioinformatic analysis and functional experiments. Analysis of differentially expressed genes (DEGs) between normal controls and NASH/HCC identified 5 hub genes (HMMR, UBE2T, TYMS, PTTG1 and GINS2). Based on the common DEGs, analyses of univariate and multivariate Cox regression and the area under the curve (AUC) value of the receiver operating characteristic (ROC) indicate that HMMR is the most significant gene associated with NASH/HCC among five hub genes. Oleate acid (OA), one of fatty acids that induce cellular adipogenesis, stimulates HMMR expression via CCAAT/enhancer-binding protein α (CEBPα). CEBPα increases the expression of HMMR through binding to its promoter. HMMR promotes HCC cell proliferation in vitro via activation of G1/S and G2/M checkpoint transitions, concomitant with a marked increase of the positive cell cycle regulators, including cyclin D1, cyclin E, and cyclin B1. Knockdown of HMMR suppresses HCC tumor growth in nude mice. Our study identifies an important role of HMMR in NASH/HCC, and suggests that HMMR may be a useful target for therapy and prognostic prediction of NASH/HCC patients.

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Section: Discussionmentioning

confidence: 99%

“…TYMS is an essential rate-limiting enzyme in the nucleotide metabolism, and is involved in DNA synthesis [40]. GINS2 knockdown also inhibits cell viability and induces cell cycle arrest in pancreatic cancer cells [41]. Thus, abnormal cell cycle may be the intrinsic related mechanism of NASH and HCC.…”

Section: Functional and Pathway Enrichment Analysismentioning

confidence: 99%

Oleate acid-stimulated HMMR expression by CEBPα is associated with nonalcoholic steatohepatitis and hepatocellular carcinoma

Zhang¹,

Liu²,

Xie³

et al. 2020

Int. J. Biol. Sci.

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show abstract

“…In recent decades, GINS2 has been involved in the development of various cancers, such as pancreatic, lung, and thyroid cancers [15,17,32]. Zhang et al demonstrated that GINS2 elevated cell growth and cell cycle progression by activating the MAPK/ERK pathway in pancreatic cancer cells [17].…”

Section: Discussionmentioning

confidence: 99%

“…GINS complex subunit 2 (GINS2) serves as an oncogene in cancer genesis by enhancing cell growth and repressing cell apoptosis in various cancers, including thyroid, lung, and pancreatic cancers [15][16][17]. It has also been associated with the progression of OC by regulating cell growth and apoptosis [18,19].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA miR-502-5p inhibits ovarian cancer genesis by downregulation of GINS complex subunit 2

et al. 2021

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Ovarian cancer (OC) is one of the most common malignancies with high incidence and mortality and the eighth most common cancer-associated mortality in women worldwide. Aberrant expression of the GINS complex subunit 2 (GINS2) gene and miR-502-5p has been associated with cancer progression. This study aims to investigate the specific molecular mechanism of the miR-502-5p-GINS2 axis in OC. GINS2 and miR-502-5p expression in OC tissues and cell lines was measured using RT-qPCR. Next, we investigated the interaction between miR-502-5p and GINS2 using a luciferase assay. The role of the miR-502-5p-GINS2 axis was detected by assessing cell proliferation, migration, and apoptosis levels, such as caspase-3 activity and caspase-3 protein expression, in the OC cell lines CaOV3 and SKOV3, respectively. MiR-502-5p expression was decreased, and GINS2 expression was dramatically elevated in OC tissues and cells. Upregulation of miR-502-5p expression repressed cellular proliferation and migration levels but increased the cellular apoptosis level. GINS2 overexpression enhanced the proliferation and migration levels but hampered OC cell apoptosis. Moreover, miR-502-5p inhibited GINS2 expression and suppressed OC tumorigenesis. miR-502-5p targeting GINS2 suppressed OC progression by inhibiting cell growth and promoting cell apoptosis. Hence, we provide a comprehensive understanding of OC involving both miR-502-5p and GINS2, which might be effective therapeutic targets for OC patients.

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“…MAPK regulates cell proliferation, differentiation, development and apoptosis through signaling transmission ( 23 , 40 ). In our previous study, it was found that GINS2 interference inhibited cell viability, induced cell cycle arrest and promoted cell apoptosis in pancreatic cancer cell lines via the MAPK/ERK pathway ( 41 ). In the present study, the relationship between GINS2 and MAPK pathway was investigated in TC cells.…”

Section: Discussionmentioning

confidence: 99%

GINS2 affects cell proliferation, apoptosis, migration and invasion in thyroid cancer via regulating MAPK signaling pathway

Zhang

et al. 2021

Mol Med Rep

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Globally, thyroid cancer (TC) is considered to be the commonest endocrine malignancy. GINS complex subunit 2 (GINS2) belongs to the GINS complex family and is associated with cellular migration, invasion and growth. The present study aimed to investigate the underlying mechanisms of GINS2 on cell viability, migration and invasion in TC cells. By using MTT, wound healing and Transwell assays, the cell viability, migration and invasion were determined. Apoptosis was examined by immunofluorescence. Western blotting was used to detect protein expression levels. In the present study, biological function analysis demonstrated that GINS2 interference attenuated cell viability, migration and invasion in TC cell lines (K1 and SW579). It was discovered that, compared with the control group, GINS2 silencing induced apoptosis in TC cells. Additionally, GINS2 interference inhibited key proteins in the MAPK signaling pathway, including JNK, ERK and p38. According to these comparative experiments, GINS2 was considered to act a pivotal part in cell viability, migration and invasion of TC by regulating the MAPK signaling pathway and might be a potential therapeutic target for treating TC.

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GINS2 affects cell viability, cell apoptosis, and cell cycle progression of pancreatic cancer cells via MAPK/ERK pathway

Cited by 17 publications

References 33 publications

Oleate acid-stimulated HMMR expression by CEBPα is associated with nonalcoholic steatohepatitis and hepatocellular carcinoma

Oleate acid-stimulated HMMR expression by CEBPα is associated with nonalcoholic steatohepatitis and hepatocellular carcinoma

MicroRNA miR-502-5p inhibits ovarian cancer genesis by downregulation of GINS complex subunit 2

GINS2 affects cell proliferation, apoptosis, migration and invasion in thyroid cancer via regulating MAPK signaling pathway

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