Abstract
BackgroundHOXD9, a Hox family member, is involved in cancer growth and metastasis. But, its regulation mechanism at the molecular level particularly in colorectal cancer (CRC), is mostly unknown.MethodsThe HOXD9 protein expression levels were analyzed using immunofluorescence, immunohistochemistry (IHC) assays, and western blot. The in vivo and in vitro roles of HOXD9 in CRC were determined using colony formation and EdU incorporation, CCK‐8, wound scratch and transwell invasion assay, and animal models.ResultsExpression of HOXD9 was higher in CRC than in matched healthy tissues. High expression of HOXD9 has significantly associated with the American Joint Committee on Cancer (AJCC) stages, tumor differentiation, lymph node metastasis, and other serious invasions, and it had a poor prognosis. In vitro, HOXD9 encouraged proliferation, movement and EMT processes in cells of CRC. Also, TGF‐β1 promoted the expression of HOXD9 and this effect was dependent on the dose and downregulation of HOXD9 repressed TGF‐β1 ‐induced EMT. In vivo, HOXD9 promoted the invasive and metastasis of CRC cells via orthotopic implantation.ConclusionsThe ectopic expression of HOXD9 promoted the invasion metastasis in cells of the colorectal tumor by induction of EMT in vitro and vivo.
Highlights
Colorectal cancer (CRC) has been a public health concern for years, and it accounts for approximately 9% of all cancer incidence rates, this represents more than 1.4 million new cases yearly.[1]
The current study suggested that increased expression of HOXD9 is associated with proliferation, invasion, and spread of the tumor and indicates poor prognosis in patients suffering from colorectal cancer (CRC)
We previously reported that HOXD9 is highly expressed in GC,[12] we determined whether HOXD9 has any effect on GC proliferation, invasion, and metastasis
Summary
Colorectal cancer (CRC) has been a public health concern for years, and it accounts for approximately 9% of all cancer incidence rates, this represents more than 1.4 million new cases yearly.[1]. The HOX proteins regulate various cellular processes by controlling the expression of several downstream target genes.[4,5]. It is common for a single homeoprotein to cause pleiotropic effects on cell behavior, such as alterations in survival, invasion, proliferation, and migration. The HOXD9 gene is an example of HOXD genes that are located close to the 3′ end of a chromosome It plays a role in the development and progression of cancer.[10,11]. Studies have suggested that HOXD9 is highly expressed in most squamous cell carcinomas of the human esophagus. The current study suggested that increased expression of HOXD9 is associated with proliferation, invasion, and spread of the tumor and indicates poor prognosis in patients suffering from CRC. Our results reported for the first time that high expression of HOXD9 could enhance the formation of aggressive characteristics of colorectal tumor cells
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