Underexpression of HOXA11 Is Associated with Treatment Resistance and Poor Prognosis in Glioblastoma

Bem, Young; Kim, Seung Hyun; Kim, Ji Young; Kim, Ja Eun; Dho, Yun Sik; Kim, Jin Wook; Kim, Yong Hwy; Woo, Hyun Goo; Kim, Se Hyuk; Kang, Sung Ho; Kim, Hak Jae; Kim, Tae Min; Lee, Sang Kun; Choi, Seung Hong; Park, Shin Young; Kim, Il Han; Kim, Dong Gyu

doi:10.4143/crt.2016.106

Cited by 36 publications

(32 citation statements)

References 49 publications

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“…Cell proliferation and cell metastasis are two main manifestation of malignancies. Thus, we determined the roles of HOXA11-AS by colony formation assay, cell cycle assay, cell proliferation assay, transwell assay and wound-healing assay, and found that knockdown of HOXA11-AS in MDA-MB-231 and MDA-MB-436 cells significantly inhibited cell proliferation and metastasis, which was consistent with other researchers' findings (16,24,25). In addition, Wang et al (18) showed that HOXA11-AS was closely associated with glioma grading and positively related with poor prognosis.…”

Section: Discussionsupporting

confidence: 87%

Long non-coding RNA HOXA11-AS promotes cell proliferation and metastasis in human breast cancer

2017

Molecular Medicine Reports

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Breast cancer is one of the most frequently occurring malignancies in female cancers worldwide, however, its detailed mechanism of tumorigenesis remains to be elucidated. Long non-coding RNAs (LncRNAs) have previously been demonstrated to be important in multiple cancers, including breast cancer. The present study aimed to elucidate the molecular mechanism of the effects of the novel Lnc RNA HOXA11‑AS, on cell proliferation and metastasis in breast cancer. The data revealed that the relative transcript level of HOXA11‑AS was upregulated in vivo and in vitro in models of breast cancer. Knockdown of HOXA11‑AS in MDA‑MB‑231 and MDA‑MB‑436 breast cancer cell lines inhibited the formation of cell colonies and arrested the cell cycle at the G0/G1 phase. Depletion of HOXA11‑AS using two specific short interfering (si)RNAs against HOXA11‑AS (siHOXA11‑AS‑1 and siHOXA11‑AS‑2) additionally suppressed the cell proliferative rate. Furthermore, transwell assays and wound‑healing analysis revealed that siRNA transfection inhibited cell migration and invasion by ~50% in the two cell lines. The results of the present study demonstrated the oncogenic role of HOXA11‑AS in breast cancer, providing novel clues for the future clinical diagnosis and treatment of early stage breast cancer patients.

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Section: Discussionsupporting

confidence: 87%

Long non-coding RNA HOXA11-AS promotes cell proliferation and metastasis in human breast cancer

2017

Molecular Medicine Reports

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“…The methylation of HOXA11 was related to the older patient as well as poor survival in GBM. Furthermore, this study discovered candidate mediators (TGFBR2, CRIM1, TXNIP, DPYSL2, and CRMP1) that may impart treatment resistance following HOXA11 suppression 33. As a conclusion, these results indicate that HOXA11‐AS plays a key role in GBM and it can be a novel therapeutic target for the treatment of GBM.…”

Section: Hoxa11‐as Lncrna In Human Cancersmentioning

confidence: 66%

HOXA11 antisense long noncoding RNA (HOXA11‐AS): A promising lncRNA in human cancers

Zhou

Xie

et al. 2018

Cancer Medicine

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The cancers are the leading cause of disease‐related deaths worldwide with a high risk of morbidity and mortality. Long noncoding RNAs (lncRNAs) play a critical role in a wide range of biological processes, including tumorigenesis. HOXA11‐AS (NCRNA00076), the antisense strands of HOXA11 gene, was initially revealed in a mouse embryonic cDNA library in 2009 and it was a fairly novel lncRNA. This review summarized the advanced research progression concerning the expression and role of HOXA11‐AS in different human malignancies. The expression of HOXA11‐AS is aberrantly altered in many cancers, either as a tumor suppressor or as a tumor accelerator. The different underlying mechanism of HOXA11‐AS in different cancers (including, nonsmall cell lung cancers, osteosarcoma, uveal melanoma, glioma, hepatocellular carcinoma, gastric cancer, breast cancer, cervical cancer, ovarian cancer, colorectal cancer, ovarian cancer, and glioblastoma) was also detailed. These findings lead us to conclude that HOXA11‐AS participate in the complex network of cancers and plays an important role in the tumorigenesis and progression. Functional HOXA11‐AS could be a promising biomarker for early detection as well as prognosis evaluation in cancer patients. Future HOXA11‐AS‐targeted intervention may become a valuable novel therapeutic tool, improving the clinical management of cancers.

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“…In addition, HOXA11 methylation has been used to predict survival outcomes for AML patients [14] and identified as a potential prognostic biomarker for ovarian cancer patients, with HOXA11 promoter methylation predicting poor outcomes in ovarian cancer [15]. Reduced expression of HOXA11 has also been linked to treatment resistance in glioblastoma, including RT [27]. These two CpGs located within the HOXA11 and ZMIZ1 gene bodies appear to be susceptible to DNA methylation changes in more than one cell line, indicating that they may be hotspots for DNA damage.…”

Section: Discussionmentioning

confidence: 99%

DNA methylation changes following DNA damage in prostate cancer cells

et al. 2019

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Many cancer therapies operate by inducing double-strand breaks (DSBs) in cancer cells, however treatment-resistant cells rapidly initiate mechanisms to repair damage enabling survival. While the DNA repair mechanisms responsible for cancer cell survival following DNA damaging treatments are becoming better understood, less is known about the role of the epigenome in this process. Using prostate cancer cell lines with differing sensitivities to radiation treatment, we analysed the DNA methylation profiles prior to and following a single dose of radiotherapy (RT) using the Illumina Infinium HumanMethylation450 BeadChip platform. DSB formation and repair, in the absence and presence of the DNA hypomethylating agent, 5-azacytidine (5-AzaC), were also investigated using γH2A.X immunofluorescence staining. Here we demonstrate that DNA methylation is generally stable following a single dose of RT; however, a small number of CpG sites are stably altered up to 14 d following exposure. While the radioresistant and radiosensitive cells displayed distinct basal DNA methylation profiles, their susceptibility to DNA damage appeared similar demonstrating that basal DNA methylation has a limited influence on DSB induction at the regions examined. Recovery from DSB induction was also similar between these cells. Treatment with 5-AzaC did not sensitize resistant cells to DNA damage, but rather delayed recruitment of phosphorylated BRCA1 (S1423) and repair of DSBs. These results highlight that stable epigenetic changes are possible following a single dose of RT and may have significant clinical implications for cancer treatment involving recurrent or fractionated dosing regimens.

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Underexpression of HOXA11 Is Associated with Treatment Resistance and Poor Prognosis in Glioblastoma

Cited by 36 publications

References 49 publications

Long non-coding RNA HOXA11-AS promotes cell proliferation and metastasis in human breast cancer

Long non-coding RNA HOXA11-AS promotes cell proliferation and metastasis in human breast cancer

HOXA11 antisense long noncoding RNA (HOXA11‐AS): A promising lncRNA in human cancers

DNA methylation changes following DNA damage in prostate cancer cells

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