Targeting HOX/PBX dimer formation as a potential therapeutic option in esophageal squamous cell carcinoma.

Homeobox genes are known to be classic examples of the intimate relationship between embryogenesis and tumorigenesis, which are a family of transcriptional factors involved in determining cell identity during early development, and also dysregulated in many malignancies. Previously, HOXB7, HOXC6 and HOXC8 were found abnormally upregulated in esophageal squamous cell carcinoma (ESCC) tissues compared with normal mucosa and seen as poor prognostic predictors for ESCC patients, and were shown to promote cell proliferation and anti-apoptosis in ESCC cells. These three HOX members have a high level of functional redundancy, making it difficult to target a single HOX gene. The aim of the present study was to explore whether ESCC cells are sensitive to HXR9 disrupting the interaction between multiple HOX proteins and their cofactor PBX, which is required for HOX functions. ESCC cell lines (KYSE70, KYSE150, KYSE450) were treated with HXR9 or CXR9, and coimmunoprecipitation and immunofluorescent colocalization were carried out to observe HOX/PBX dimer formation. To further investigate whether HXR9 disrupts the HOX pro-oncogenic function, CCK-8 assay and colony formation assay were carried out. Apoptosis was assessed by flow cytometry, and tumor growth in vivo was investigated in a xenograft model. RNA-seq was used to study the transcriptome of HXR9-treated cells. Results showed that HXR9 blocked HOX/PBX interaction, leading to subsequent transcription alteration of their potential target genes, which are involved in JAK-signal transducer and activator of transcription (STAT) activation and apoptosis inducement. Meanwhile, HXR9 showed an antitumor phenotype, such as inhibiting cell proliferation, inducing cell apoptosis and significantly retarding tumor growth. Therefore, it is suggested that targeting HOX/PBX may be a novel effective treatment for ESCC.

The survival predictive significance of HOXC6 and HOXC8 in esophageal squamous cell carcinoma.

BACKGROUND & AIM: Esophageal squamous cell carcinoma (ESCC), a common disease in China, is mainly treated surgically. We established a prospective database of patients with esophageal cancer between January 2000 and December 2010, including 486 subjects with ESCC who underwent surgical treatment. In this study, we explored the prognostic significance of the expressions of HOXC6 and HOXC8, responsible for embryonic development, by studying the specimens collected from clinical subjects during strict follow-up periods. MATERIALS & METHODS: Immunohistochemistry was used to detect the expressions of HOXC6 and HOXC8 in 274 ESCC subjects including 138 ESCC subjects treated with surgery alone and 136 ESCC subjects treated with neoadjuvant chemotherapy. Survival analysis was performed from the day of surgery to August 2013. RESULTS: The 5-y survival rate of the 274 ESCC subjects was 44.2%, with a median survival time of 44.12 mo. For the 274 ESCC subjects involved in the investigation of HOXC6 and HOXC8 expressions, the median survival time of subjects with high-level expressions of HOXC6 and HOXC8 was shorter than that for subjects with low-level expressions (P = 0.001, P < 0.001, respectively). Similar results were obtained from the analysis of the prognostic value of HOXC6 and HOXC8 in the group treated with surgery alone and the group treated with neoadjuvant chemotherapy. Multivariate analysis demonstrated that HOXC6 and HOXC8 expressions were independent prognostic factors in patients with ESCC. CONCLUSIONS: The HOXC6 and HOXC8 genes can be used as prognostic markers in patients with ESCC, but prospective studies are still needed to confirm.

[Study on vibrational spectra of ethyl hexanoate molecule].

The vibrational spectra of ethyl hexanoate were calculated by the density functional theory (DFT) with B3LYP complex function, diffuse function and polarization function added to heavy atoms and light atoms. On the base of this, the normal Raman spectrum (NRS) and the infrared spectrum (IR) were assigned in detail in the present paper. Comparing the calculated results with the experimental data, the calculated results are in good agreement with the experimental results. The comparison of the experimental Raman and infrared spectra shows that in the experimental Raman spectrum, the strongest bands appear at the frequencies of 2600-3100 cm(-1), while the strongest band is not 1734 cm(-1) but 1444 cm(-1) at the frequencies of 400-2000 cm(-1). The band 1734 cm(-1) attributed to the C=O stretch vibration is the distinctive mark of organic ester compounds, and the band 1444 cm(-1) is related to the symmetric and anti-symmetric scissors vibration of C-H. In the experimental infrared spectrum, the strongest vibrational band is 1739 cm(-1), which is related to C=O stretch vibration; At the frequencies of 400-2000 cm(-1), the relative intensity of the infrared spectrum is distinctively stronger than that of the Raman spectrum, but the relative intensity of infrared spectrum is weaker than that of the Raman spectrum at the frequencies of 2600-3100 cm(-1). In the frequencies of 2600-2800 cm(-1), the vibrational bands 2762 and 2732 cm(-1) do not appear in the experimental spectra, which may originate from two reasons: (1) the weak interaction of molecules. Also, the relative intensity of these vibrational bands is very weak in the experimental spectra, and this may testify that the interaction of molecules is rather weak; (2) the vibrational bands may belong to second order vibrational mode at the frequencies of 2600-2800 cm(-1). The relative intensity of infrared bands is weaker than that of the Raman bands at the frequencies of 2600-2800 cm(-1). At the end, the stronger bands appearing in Raman and infrared experimental spectra are assigned as characteristic marks, respectively. The study on vibrational spectra of ethyl hexanoate molecule may have great application value in detection of liquor flavor, chemical industry and biology fields, providing important reference value for the related basic research field.