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HOXA10 induces BCL2 expression, inhibits apoptosis, and promotes cell proliferation in gastric cancer.

ABSTRACT: Homeobox A10 (HOXA10) has been implicated critical for the promotion of carcinogenesis, but the underlying mechanism between HOXA10 and malignant gastric cancer (GC) phenotype remains elusive. In the present study, we analyzed and validated that HOXA10 and BCL2 expressions were elevated both at the mRNA and protein levels in GC tissues. Upregulated HOXA10 promoted GC cell proliferation with reduced apoptosis in vitro and accelerated GC tumor growth in vivo. Bioinformatics analysis and quantitative real-time polymerase chain reaction (qRT-PCR) experiment inferred that HOXA10 might upregulate the expression of BCL2. By performing western blot, chromatin immunoprecipitation and quantitative PCR (ChIP-qPCR), and rescue experiment, we found that HOXA10 might bind to BCL2 promoter region, induce its expression, and thus inhibit intrinsic apoptosis pathway. Moreover, higher expression of HOXA10 and BCL2 predicted poor overall survival (OS) in GC patients. In summary, our study indicated that HOXA10 was upregulated in GC, and that HOXA10 might promote cell proliferation by elevating BCL2 expression and inhibiting apoptosis.

SUBMITTER: Song C

PROVIDER: S-EPMC6745829 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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HOXA10 induces BCL2 expression, inhibits apoptosis, and promotes cell proliferation in gastric cancer.

Song Chenlong C Han Yang Y Luo Huan H Qin Zhiwei Z Chen Zhengqian Z Liu Yuan Y Lu Su S Sun Huimin H Zhou Chongzhi C

Cancer medicine 20190730 12

Homeobox A10 (HOXA10) has been implicated critical for the promotion of carcinogenesis, but the underlying mechanism between HOXA10 and malignant gastric cancer (GC) phenotype remains elusive. In the present study, we analyzed and validated that HOXA10 and BCL2 expressions were elevated both at the mRNA and protein levels in GC tissues. Upregulated HOXA10 promoted GC cell proliferation with reduced apoptosis in vitro and accelerated GC tumor growth in vivo. Bioinformatics analysis and quantitati ...[more]

PMID: 31364281

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Project description:BackgroundmiR-100 has been reported to closely associate with gastric cancer (GC) initiation and progression. However, the underlying mechanism of miR-100-3p in GC is still largely unclear. In this study, we intend to study how miR-100-3p regulates GC malignancy.MethodsThe expression levels of miR-100-3p in vitro (GES-1 and GC cell lines) and in vivo (cancerous and normal gastric tissues) were examined by quantitative real-time PCR (qRT-PCR). MTT and PE/Annexin V analyses were responsible for measurement of the effects of miR-100-3p on GC cell proliferation and apoptosis. Transwell assay with or without matrigel was used to examine the capacity of migration and invasion in GC cells. The interaction of miR-100-3p with bone morphogenetic protein receptor 2 (BMPR2) was confirmed through transcriptomics analysis and luciferase reporter assay. qRT-PCR and Western blot analyses were applied to determine the expression of ERK/AKT and Bax/Bcl2/Caspase3, which were responsible for the dysfunction of miR-100-3p.ResultsmiR-100-3p was down-regulated in GC cell lines and cancerous tissues, and was negatively correlated with BMPR2. Loss of miR-100-3p promoted tumor growth and BMPR2 expression. Consistently, the effects of miR-100-3p inhibition on GC cells were partially neutralized by knockdown of BMPR2. Over-expression of miR-100-3p simultaneously inhibited tumor growth and down-regulated BMPR2 expression. Consistently, over-expression of BMPR2 partially neutralized the effects of miR-100-3p over-expression. Further study demonstrated that BMPR2 mediated the effects downstream of miR-100-3p, which might indirectly regulate ERK/AKT and Bax/Bcl2/Caspase3 signaling pathways.ConclusionmiR-100-3p acted as a tumor-suppressor miRNA that down-regulated BMPR2, which consequently inhibited the ERK/AKT signaling and activated Bax/Bcl2/Caspase3 signaling. This finding provided novel insights into GC and could contribute to identify a new diagnostic and therapeutic target.

Dataset Information

HOXA10 induces BCL2 expression, inhibits apoptosis, and promotes cell proliferation in gastric cancer.

Publications

HOXA10 induces BCL2 expression, inhibits apoptosis, and promotes cell proliferation in gastric cancer.

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