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转录因子 BHLHE40 介导的 INHBA 上调促进结肠癌细胞增殖和迁移。

Upregulation of INHBA mediated by the transcription factor BHLHE40 promotes colon cancer cell proliferation and migration.

机构信息

Department of Colorectal Surgery, The Affiliated Lihuili Hospital, Ningbo University, Ningbo, China.

Department of Radiation Oncology, The Affiliated Lihuili Hospital, Ningbo University, Ningbo, China.

出版信息

J Clin Lab Anal. 2022 Jul;36(7):e24539. doi: 10.1002/jcla.24539. Epub 2022 Jun 11.

Abstract

BACKGROUND

Colon cancer is highly prevalent, and cell proliferation and migration are major reasons for its progression to malignancy. The upregulation of INHBA, a glycoprotein hormone that regulates the secretion of pituitary hormones, is documented to be oncogenic in numerous cancers, consisting of breast, gastric, and ovarian cancer. Herein, we assessed the role of INHBA in the proliferation along with the migration of colon cancer cells.

METHODS

TCGA datasets were used to assess INHBA expression and its correlation with prognosis in colon cancer patients. Analyses on JASPAR, PROMO, and ENCODE databases, uncovered high correlation between INHBA and BHLHE40. Western blot and RT-qPCR analysis were used to determine protein and mRNA levels. Cell transfection inhibited the expression of INHBA and BHLHE40. Cell proliferation rates were determined using CCK8 analysis. Wound healing assays were adopted to explore cell migration.

RESULTS

INHBA is markedly elevated in colon cancer tissues along with cells and is a predictive factor for patient's prognosis with colon cancer. INHBA silencing suppressed colon cancer cell proliferation and migration. Furthermore, we confirmed the association of INHBA with BHLHE40 in colon cancer cells. BHLHE40 could directly modulates INHBA expression. Here, we show that BHLHE40 modulates the expression of INHBA, which influences the proliferation, and migration of colon cancer cells.

CONCLUSION

INHBA acts as an oncogene in colon cancer and it can be regulated by the transcription factor BHLHE40.

摘要

背景

结肠癌发病率较高,细胞增殖和迁移是其恶性进展的主要原因。INHBA 是一种调节垂体激素分泌的糖蛋白激素,其上调已被证明在多种癌症中具有致癌作用,包括乳腺癌、胃癌和卵巢癌。在此,我们评估了 INHBA 在结肠癌细胞增殖和迁移中的作用。

方法

使用 TCGA 数据集评估 INHBA 在结肠癌患者中的表达及其与预后的相关性。通过 JASPAR、PROMO 和 ENCODE 数据库的分析,发现 INHBA 与 BHLHE40 之间具有高度相关性。Western blot 和 RT-qPCR 分析用于确定蛋白和 mRNA 水平。细胞转染抑制 INHBA 和 BHLHE40 的表达。使用 CCK8 分析测定细胞增殖率。采用划痕愈合实验探讨细胞迁移。

结果

INHBA 在结肠癌组织和细胞中明显升高,是结肠癌患者预后的预测因素。INHBA 沉默抑制结肠癌细胞的增殖和迁移。此外,我们证实了 INHBA 与结肠癌细胞中 BHLHE40 的关联。BHLHE40 可以直接调节 INHBA 的表达。在这里,我们表明 BHLHE40 调节 INHBA 的表达,从而影响结肠癌细胞的增殖和迁移。

结论

INHBA 在结肠癌中起癌基因作用,可被转录因子 BHLHE40 调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1905/9279979/4c2b674e7986/JCLA-36-e24539-g004.jpg

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