Increased HOXC6 expression predicts chemotherapy sensitivity in patients with esophageal squamous cell carcinoma

Shen, Luyan; Fan, Mingxia; Dong, Bin; Yan, Wanpu; Chen, Ke‐Neng

doi:10.3892/ol.2017.6772

Cited by 6 publications

(6 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High expression of HOXA10 was predictive of resistance of temozolomide treatment in glioblastoma through regulation of the homologous recombinant DNA repair pathway 10 . Increased HOXC6 expression predicted chemotherapy sensitivity in patients with ESCC 29 . HOXA13 expression increased cisplatin resistance in ESCC cells by promoting EMT 30 .…”

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

HOXB7 mediates cisplatin resistance in esophageal squamous cell carcinoma through involvement of DNA damage repair

Zhou

Dong

et al. 2019

Thoracic Cancer

Self Cite

View full text Add to dashboard Cite

Background DNA damage repair is an important mechanism of platinum resistance. HOXB7 is one member of HOX family genes, which are essential developmental regulators and frequently dysregulated in cancer. Recently, its relevance in chemotherapy resistance and DNA damage repair has also been addressed. However, little is known regarding the association between HOXB7 and chemotherapy resistance in esophageal squamous cell carcinoma (ESCC). Methods The association between HOXB7 expression detected by immunohistochemisty and tumor regression grade (TRG) and long‐term survival was analyzed in 143 ESCC patients who underwent neoadjuvant chemotherapy. CCK8 assay was used to examine the effect of cisplatin in a panel of four ESCC cell lines. A stable cell strain with HOXB7 knockdown of KYSE150 and KYSE450 was established to explore the effect on cisplatin sensitivity. The interaction of HOXB7 with Ku70, Ku80 and DNA‐PKcs was determined by GST‐pull down, coimmunoprecipitation and immunofluorescent colocalization. Finally, we investigated whether disrupting HOXB7 function by a synthetic peptide HXR9 blocking the formation of HOXB7/PBX could enhance cisplatin sensitivity in vitro and in vivo. Results High expression of HOXB7 was associated with cisplatin resistance and worse chemotherapy efficacy. HOXB7 knockdown reinforced cisplatin sensitivity. It was identified that HOXB7 interacts with Ku70, Ku80 and DNA‐PKcs. HOXB7 knockdown was related to the downregulation of Ku70, Ku80 and DNA‐PKcs as well as arrested cell cycle in S phase. HOXB7 inhibition by HXR9 had a synergistic effect to improve cisplatin sensitivity. Conclusion HOXB7 may be a biomarker for the prediction of chemoresistance of ESCC and serves as a promising therapeutic target.

show abstract

Section: Discussionmentioning

confidence: 97%

“…10 Increased HOXC6 expression predicted chemotherapy sensitivity in patients with ESCC. 29 HOXA13 expression increased cisplatin resistance in ESCC cells by promoting EMT. 30 HOXA1 might be able to act as a predictive marker of chemosensitivity.…”

Section: Disrupting Hoxb7 Function Sensitizes Escc Cells To Cisplatinmentioning

confidence: 95%

HOXB7 mediates cisplatin resistance in esophageal squamous cell carcinoma through involvement of DNA damage repair

Zhou

Dong

et al. 2019

Thoracic Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…Previous studies demonstrated that HOXC6 promoted cancer proliferation, migration, and chemoresistance Shen, Fan, Dong, Yan, & Chen, 2017;Sui et al, 2016). However, its role in TNBC was largely unknown.…”

Section: The Oncogenic Role Of Linc00339 Is Mediated By Regulating mentioning

confidence: 95%

Long noncoding RNA Linc00339 promotes triple‐negative breast cancer progression through miR‐377‐3p/HOXC6 signaling pathway

Wang

Chen

Zhang

et al. 2019

Journal Cellular Physiology

View full text Add to dashboard Cite

Recently, long noncoding RNAs (lncRNAs) have become the key gene regulators and prognostic biomarkers in various cancers. Through microarray data, Linc00339 was identified as a candidate oncogenic lncRNA. We compared the expression levels of Linc00339 in several breast cancer cell lines and normal mammary gland epithelial cell line. The effects of Linc00339 on tumor progression were examined both in vitro and in vivo. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays were applied to evaluate the functions of Linc00339, miR‐377‐3p, and HOXC6 on cell proliferation. Flow cytometry analysis was used to detect apoptosis and cell cycle distribution. Overall survival (OS) was analyzed using data from The Cancer Genome Atlas and molecular taxonomy of breast cancer international consortium (METABRIC). Dual luciferase assay and RNA immunoprecipitation were performed to confirm the interaction between Linc003339 and miR‐377‐3p. Linc00339 was increased in breast cancer cell lines compared with the normal epithelial cell. Through in vitro and in vivo experiments, Linc00339 overexpression promoted triple‐negative breast cancer (TNBC) proliferation, inhibited cell cycle arrest, and suppressed apoptosis. Silencing of Linc00339 obtained the opposite effects. Mechanistic investigations demonstrated that Linc00339 could sponge miR‐377‐3p and regulate its expression. Higher expression of miR‐377‐3p indicated longer OS in breast cancer patients, especially in TNBC patients. Overexpression of miR‐377‐3p retarded TNBC cell growth through regulating cell cycle distribution and apoptosis. And miR‐377‐3p was involved in Linc00339‐mediated TNBC proliferation through regulating HOXC6 expression. Knockdown of HOXC6 inhibited TNBC progression. In conclusion, our results illuminated that the novel Linc00339/miR‐377‐3p/HOXC6 axis played a critical role in TNBC progression and might be a promising therapeutic target for TNBC treatment.

show abstract

“…The highly conserved HOX gene family, which was originally discovered in drosophila, is critical to embryonic development and encodes transcription factors that regulate cell proliferation and differentiation . Alterations in the expression patterns of HOX genes cause dysregulation of HOX protein function leading to abnormal proliferation and differentiation . Several studies have explored the expression of HOX genes, particularly HOXA13 , which contribute to tumorigenesis in a variety of tumors .…”

Section: Introductionmentioning

confidence: 99%

“…6 Alterations in the expression patterns of HOX genes cause dysregulation of HOX protein function leading to abnormal proliferation and differentiation. 7 Several studies have explored the expression of HOX genes, particularly HOXA13, which contribute to tumorigenesis in a variety of tumors. [8][9][10][11] Our previous studies determined that HOXA13 is overexpressed in ESCC but not in normal tissues, indicating that HOXA13 may play a crucial role in the tumorigenesis and development of ESCC.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of HOXA13 sensitizes human esophageal squamous cell carcinoma to chemotherapy

et al. 2018

Self Cite

View full text Add to dashboard Cite

BackgroundChemoresistance often develops in esophageal squamous cell carcinoma (ESCC), leading to poor prognosis. HOX genes play a crucial role in embryonic development and cell differentiation. Studies have recently linked HOX with chemoresistance, thus we explored whether HOXA13 is involved in ESCC chemoresistance.MethodsOne hundred thirty‐one ESCC patients who received neoadjuvant chemotherapy were enrolled. HOXA13 expression was examined by immunohistochemistry. RNA interference was used to knock down the HOXA13 expression in KYSE70 and transfected HOXA13 plasmid to overexpress HOXA13 in KYSE510 cells. We examined half‐maximal inhibitory concentration of cisplatin, apoptosis, and epithelial‐to‐mesenchymal transition (EMT) in ESCC cell lines with different HOXA13 expression levels by cell counting kit‐8, flow cytometry, and transwell analysis.ResultsThe median survival of patients with high HOXA13 expression was significantly shorter than those with low expression (P = 0.027). HOXA13 was associated with worse tumor regression grade (P = 0.009). Low HOXA13 expressed cells decreased the half‐maximal inhibitory concentration of cisplatin (P < 0.05), increased cisplatin‐induced apoptosis (P < 0.05), and decreased EMT (P < 0.05) compared with high HOXA13 expressed cells. In low HOXA13 expressed cells, cleaved caspase‐3 and cleaved PARP expression induced by cisplatin increased, while expression of E‐cadherin and Snail protein, markers of EMT, was upregulated and downregulated, respectively. EMT decreased in low HOXA13 expressed cells.ConclusionHigh HOXA13 expression was associated with inferior tumor regression grade and poor overall survival in ESCC patients treated with neoadjuvant chemotherapy. HOXA13 increased cisplatin‐resistance and promoted EMT in ESCC cells.

show abstract

Increased HOXC6 expression predicts chemotherapy sensitivity in patients with esophageal squamous cell carcinoma

Cited by 6 publications

References 25 publications

HOXB7 mediates cisplatin resistance in esophageal squamous cell carcinoma through involvement of DNA damage repair

HOXB7 mediates cisplatin resistance in esophageal squamous cell carcinoma through involvement of DNA damage repair

Long noncoding RNA Linc00339 promotes triple‐negative breast cancer progression through miR‐377‐3p/HOXC6 signaling pathway

Downregulation of HOXA13 sensitizes human esophageal squamous cell carcinoma to chemotherapy

Contact Info

Product

Resources

About