Upregulation of heme oxygenase-1 in colorectal cancer patients with increased circulation carbon monoxide levels, potentially affects chemotherapeutic sensitivity

Yin, Han; Fang, Jun; Лонг, Линг; Maeda, Hiroshi; Qi, Shijie

doi:10.1186/1471-2407-14-436

Cited by 82 publications

(77 citation statements)

References 51 publications

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“…In the HO-1-positive group, there was increased HO-1-expressing macrophages in not well-differentiated tubular adenocarcinoma (tub1) among histological types. This result was not similar to that reported by Yin et al [33]. However, there was no significant difference among histological type in the present study.…”

Section: Discussioncontrasting

confidence: 57%

“…PubMed literature records indicate that the expression of HO-1 in colorectal cancer was reported in only 4 publications [28,[32][33][34]. Kang et al [32] evaluated HO-1 protein expression levels and enzyme activity using western blotting and enzyme immunoassay and found that HO-1 protein expression and enzyme activity are higher in colonic cancer tissues than in normal tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Kang et al [32] evaluated HO-1 protein expression levels and enzyme activity using western blotting and enzyme immunoassay and found that HO-1 protein expression and enzyme activity are higher in colonic cancer tissues than in normal tissues. Yin et al [33] immunohistochemically analyzed HO-1 expression in cancer cells, and increased HO-1 expression was observed in well-differentiated adenocarcinoma (tub1) than in moderately (tub2) and poorly differentiated adenocarcinoma (por). Furthermore, cytoplasmic HO-1 expression was observed well-differentiated adenocarcinoma, and nuclear HO-1 expression was observed in the moderately and poorly adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

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Increasing Heme Oxygenase-1-Expressing Macrophages Indicates a Tendency of Poor Prognosis in Advanced Colorectal Cancer

Kimura¹,

Aung²,

Ohe³

et al. 2019

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Background: Many cancers express heme oxygenase-1 (HO-1) at a higher frequency than healthy tissues, and this elevated expression is associated with cancer prognosis. Here, we aim to clarify the correlation between HO-1-expressing macrophage numbers and clinicopathological parameters of advanced colorectal cancer. Materials and Methods: Formalin-fixed and paraffin-embedded tissues of patients with advanced colorectal cancer were used. To detect HO-1 expression in macrophages, immunohistochemistry was performed. The number of positive cells was measured. Furthermore, HO-1 mRNA in colorectal cancer was examined by reverse transcription polymerase chain reaction. Results: Among the HO-1-negative and HO-1-positive groups, 58.02 and 85.00% of cases, respectively, were positive for lymph node metastasis. The disease-free survival (DFS) time was significantly shorter (p < 0.05) in the HO-1-positive group (2.44 years) than in the HO-1-negative group (4.09 years). However, according to the Cox proportional-hazards regression model, the HO-1-positive group could not be a risk factor of poor prognosis. HO-1 mRNA expression was confirmed in colorectal normal and cancer tissues. Conclusion: In this study, the correlation between HO-1-expressing macrophages and clinicopathological parameters in the tumor microenvironment of colorectal cancer was studied for the first time, and the expression was associated with lymph node metastasis and shortening of DFS.

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Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Increasing Heme Oxygenase-1-Expressing Macrophages Indicates a Tendency of Poor Prognosis in Advanced Colorectal Cancer

Kimura¹,

Aung²,

Ohe³

et al. 2019

Digestion

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“…29,30 In particular, protective autophagy plays a key role in the THP resistance of cancer cells. Moreover, THP and its prodrug epirubicin induce a cytoprotective autophagy response in bladder cancer cells 10 and breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Targeting the MIR34C-5p-ATG4B-autophagy axis enhances the sensitivity of cervical cancer cells to pirarubicin

Yan

et al. 2016

Autophagy

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Pirarubicin (THP) is a newer generation anthracycline anticancer drug. In the clinic, THP and THP-based combination therapies have been demonstrated to be effective against various tumors without severe side effects. However, previous clinical studies have shown that most patients with cervical cancer are not sensitive to THP treatment, and the associated mechanisms are not clear. Consistent with the clinical study, we confirmed that cervical cancer cells were resistant to THP in vitro and in vivo. Our data demonstrated that THP induced a protective macroautophagy/autophagy response in cervical cancer cells, and suppression of this autophagy dramatically enhanced the cytotoxicity of THP. By scanning the mRNA level change of autophagy-related genes, we found that the upregulation of ATG4B (autophagyrelated 4B cysteine peptidase) plays an important role in THP-induced autophagy. Moreover, THP increased the mRNA level of ATG4B in cervical cancer cells by promoting mRNA stability without influencing its transcription. Furthermore, THP triggered a downregulation of MIR34C-5p, which was associated with the upregulation of ATG4B and autophagy induction. Overexpression of MIR34C-5p significantly decreased the level of ATG4B and attenuated autophagy, accompanied by enhanced cell death and apoptosis in THP-treated cervical cancer cells. These results for the first time reveal the presence of a MIR34C-5p-ATG4B-autophagy signaling axis in THP-treated cervical cancer cells in vitro and in vivo, and the axis, at least partially, accounts for the THP nonsensitivity in cervical cancer patients. This study may provide a new insight for improving the chemotherapeutic effect of THP, which may be beneficial to the further clinical application of THP in cervical cancer treatment.

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“…CRC with Hmox1 expression has a lower rate of lymphatic tumor invasion and better survival than that without [13]. Well-differentiated CRC seems to have more total but less nuclear Hmox1 expression than moderately/poorly differentiated CRC [14]. The role of Hmox1 and its interaction with the Nrf2 pathway in CRC remains uncertain.…”

Section: Introductionmentioning

confidence: 99%

The Ratio of Hmox1/Nrf2 mRNA Level in the Tumor Tissue Is a Predictor of Distant Metastasis in Colorectal Cancer

et al. 2016

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Heme oxygenase 1 (Hmox1) plays an important role in the growth and spread of tumor, and its expression is regulated positively by Nrf2 [nuclear factor (erythroid-derived 2)-like 2; NFE2L2] and negatively by kelch-like ECH-associated protein 1 (Keap1) and by BTB and CNC homology 1 (Bach1). Both Hmox1 and Nrf2 contribute to distant metastasis of cancer. The mRNA levels of Hmox1, Nrf2, Keap1, and Bach1 in the tumor and normal tissues of 84 subjects with colorectal cancer (CRC) were determined by real-time polymerase chain reaction. The tumor had lower Hmox1 but higher Bach1 mRNA levels than the normal tissue. The correlations of Hmox1 with components of the Nrf2 pathway were not significant in the tumor tissue of CRC subjects with distant metastasis. The ratio of Hmox1/Nrf2 mRNA level (by percentage) in the tumor tissue was lower in the subjects with distant metastasis (97.4% (84.4–111.1%)) than in those without (101.0% (92.7–136.5%)) and was a predictor for distant metastasis in CRC (odds ratio: 0.83; 95% confidence interval: 0.68–0.97) along with serum carcinoembryonic antigen (1.0027, 1.006–1.064). The mRNA level of Hmox1 in the tumor tissue of CRC is not correlated with that of the Nrf2 pathway molecules, and its ratio to the Nrf2 level may be useful for suggesting distant metastasis in CRC.

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Upregulation of heme oxygenase-1 in colorectal cancer patients with increased circulation carbon monoxide levels, potentially affects chemotherapeutic sensitivity

Cited by 82 publications

References 51 publications

Increasing Heme Oxygenase-1-Expressing Macrophages Indicates a Tendency of Poor Prognosis in Advanced Colorectal Cancer

Increasing Heme Oxygenase-1-Expressing Macrophages Indicates a Tendency of Poor Prognosis in Advanced Colorectal Cancer

Targeting the MIR34C-5p-ATG4B-autophagy axis enhances the sensitivity of cervical cancer cells to pirarubicin

The Ratio of Hmox1/Nrf2 mRNA Level in the Tumor Tissue Is a Predictor of Distant Metastasis in Colorectal Cancer

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