Overexpression of Hypermethylated Homeobox A11 (HOXA11) Inhibits Tumor Cell Growth and Induces Apoptosis in Cervical Cancer
This study aimed to elucidate the potential of Homeobox A11 (HOXA11) as a therapeutic target and a diagnostic methylation marker for cervical cancer. Gene expression analysis using cDNA microarray in cervical cancer cell lines revealed significantly reduced expression of the HOXA11 gene. Subsequent...
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| Published in | Balsaeng'gwa saengsig Vol. 28; no. 2; pp. 37 - 45 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
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Korea (South)
Korean Society of Developmental Biology
01.06.2024
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| Online Access | Get full text |
| ISSN | 2465-9525 2465-9541 |
| DOI | 10.12717/DR.2024.28.2.37 |
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| Abstract | This study aimed to elucidate the potential of Homeobox A11 (HOXA11) as a therapeutic target and a diagnostic methylation marker for cervical cancer. Gene expression analysis using cDNA microarray in cervical cancer cell lines revealed significantly reduced expression of the HOXA11 gene. Subsequent investigation of HOXA11 promoter methylation in samples from normal individuals and invasive cervical cancer patients showed over 53.2% higher methylation in cancer scrapes compared to normal scrapes. Furthermore, overexpression of HOXA11, which is downregulated in cervical cancer, strongly suppressed cell growth in cervical cancer cell lines, HeLa and HT3. Additionally, we performed transferase dUTP nick end labeling assay and confirmed that the inhibition of cervical cancer cell proliferation occurred via apoptosis. Mechanistically, overexpression of HOXA11 led to mitochondrial apoptosis characterized by PARP cleavage due to increased c-Myc and enhanced cytochrome C secretion into the cytoplasm. These findings suggest that HOXA11 could potentially serve as a methylation marker for diagnosing cervical cancer and as a novel therapeutic target for its treatment. |
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| AbstractList | This study aimed to elucidate the potential of Homeobox A11 (HOXA11) as a
therapeutic target and a diagnostic methylation marker for cervical cancer. Gene
expression analysis using cDNA microarray in cervical cancer cell lines revealed
significantly reduced expression of the HOXA11 gene. Subsequent investigation of
HOXA11 promoter methylation in samples from normal individuals and invasive
cervical cancer patients showed over 53.2% higher methylation in cancer
scrapes compared to normal scrapes. Furthermore, overexpression of HOXA11, which
is downregulated in cervical cancer, strongly suppressed cell growth in cervical
cancer cell lines, HeLa and HT3. Additionally, we performed transferase dUTP
nick end labeling assay and confirmed that the inhibition of cervical cancer
cell proliferation occurred via apoptosis. Mechanistically, overexpression of
HOXA11 led to mitochondrial apoptosis characterized by PARP cleavage due to
increased c-Myc and enhanced cytochrome C secretion into the cytoplasm. These
findings suggest that HOXA11 could potentially serve as a methylation marker for
diagnosing cervical cancer and as a novel therapeutic target for its
treatment. This study aimed to elucidate the potential of Homeobox A11 (HOXA11) as a therapeutic target and a diagnostic methylation marker for cervical cancer. Gene expression analysis using cDNA microarray in cervical cancer cell lines revealed significantly reduced expression of the HOXA11 gene. Subsequent investigation of HOXA11 promoter methylation in samples from normal individuals and invasive cervical cancer patients showed over 53.2% higher methylation in cancer scrapes compared to normal scrapes. Furthermore, overexpression of HOXA11, which is downregulated in cervical cancer, strongly suppressed cell growth in cervical cancer cell lines, HeLa and HT3. Additionally, we performed transferase dUTP nick end labeling assay and confirmed that the inhibition of cervical cancer cell proliferation occurred via apoptosis. Mechanistically, overexpression of HOXA11 led to mitochondrial apoptosis characterized by PARP cleavage due to increased c-Myc and enhanced cytochrome C secretion into the cytoplasm. These findings suggest that HOXA11 could potentially serve as a methylation marker for diagnosing cervical cancer and as a novel therapeutic target for its treatment. This study aimed to elucidate the potential of Homeobox A11 (HOXA11) as a therapeutic target and a diagnostic methylation marker for cervical cancer. Gene expression analysis using cDNA microarray in cervical cancer cell lines revealed significantly reduced expression of the HOXA11 gene. Subsequent investigation of HOXA11 promoter methylation in samples from normal individuals and invasive cervical cancer patients showed over 53.2% higher methylation in cancer scrapes compared to normal scrapes. Furthermore, overexpression of HOXA11, which is downregulated in cervical cancer, strongly suppressed cell growth in cervical cancer cell lines, HeLa and HT3. Additionally, we performed transferase dUTP nick end labeling assay and confirmed that the inhibition of cervical cancer cell proliferation occurred via apoptosis. Mechanistically, overexpression of HOXA11 led to mitochondrial apoptosis characterized by PARP cleavage due to increased c-Myc and enhanced cytochrome C secretion into the cytoplasm. These findings suggest that HOXA11 could potentially serve as a methylation marker for diagnosing cervical cancer and as a novel therapeutic target for its treatment.This study aimed to elucidate the potential of Homeobox A11 (HOXA11) as a therapeutic target and a diagnostic methylation marker for cervical cancer. Gene expression analysis using cDNA microarray in cervical cancer cell lines revealed significantly reduced expression of the HOXA11 gene. Subsequent investigation of HOXA11 promoter methylation in samples from normal individuals and invasive cervical cancer patients showed over 53.2% higher methylation in cancer scrapes compared to normal scrapes. Furthermore, overexpression of HOXA11, which is downregulated in cervical cancer, strongly suppressed cell growth in cervical cancer cell lines, HeLa and HT3. Additionally, we performed transferase dUTP nick end labeling assay and confirmed that the inhibition of cervical cancer cell proliferation occurred via apoptosis. Mechanistically, overexpression of HOXA11 led to mitochondrial apoptosis characterized by PARP cleavage due to increased c-Myc and enhanced cytochrome C secretion into the cytoplasm. These findings suggest that HOXA11 could potentially serve as a methylation marker for diagnosing cervical cancer and as a novel therapeutic target for its treatment. |
| Author | Oh, Tae Jeong An, Sungwhan Lee, Seung-Yul Lee, Seung-Hoon |
| Author_xml | – sequence: 1 givenname: Seung-Yul orcidid: 0009-0002-4047-3593 surname: Lee fullname: Lee, Seung-Yul – sequence: 2 givenname: Tae Jeong orcidid: 0000-0001-6212-1949 surname: Oh fullname: Oh, Tae Jeong – sequence: 3 givenname: Sungwhan orcidid: 0000-0001-8781-4186 surname: An fullname: An, Sungwhan – sequence: 4 givenname: Seung-Hoon orcidid: 0000-0001-9409-1422 surname: Lee fullname: Lee, Seung-Hoon |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/39055103$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.2217/epi.14.92 10.1007/978-1-59745-522-0_15 10.1002/jbt.21455 10.1002/ijc.24745 10.32607/actanaturae.11822 10.1136/jmg.38.5.285 10.1155/2018/3569493 10.1038/sj.onc.1205651 10.1038/nrm2952 10.3390/cancers11040528 10.1002/ijc.23563 10.1016/S0065-230X(08)60702-2 10.1038/npp.2012.112 10.1016/S0008-6363(99)00384-3 10.1038/s41556-024-01429-4 10.18632/oncotarget.16528 10.62347/HJKI7733 10.1016/0092-8674(83)90092-2 10.1016/S2214-109X(22)00501-0 |
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| Keywords | Methylation marker Homeobox A11 (HOXA11) Cervical cancer Apoptosis |
| Language | English |
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| Snippet | This study aimed to elucidate the potential of Homeobox A11 (HOXA11) as a therapeutic target and a diagnostic methylation marker for cervical cancer. Gene... This study aimed to elucidate the potential of Homeobox A11 (HOXA11) as a therapeutic target and a diagnostic methylation marker for cervical cancer. Gene... |
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| Title | Overexpression of Hypermethylated Homeobox A11 (HOXA11) Inhibits Tumor Cell Growth and Induces Apoptosis in Cervical Cancer |
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