Homeobox (HOX) C9, a member of the HOX family, is an important transcription factor, and it plays a significant role in various biological processes. This family of genes is highly valued for their essential roles in establishing and maintaining the body axis during embryonic development and adult tissues. Further, HOXC9 plays a central role in neuronal differentiation, angiogenesis, and adipose distribution, which are essential for the development of the nervous system, maturation of tissues and organs, and maintenance of energy balance and metabolic health. Recent research has found that abnormal HOXC9 expression is closely associated with the development and progression of various tumor types. The HOXC9 expression level can be an indicator of tumor prognosis. Therefore, elucidating the association between HOXC9 expression and its regulatory mechanisms and tumorigenesis can provide novel insights on the diagnosis and treatment of patients with cancer.

Endometrial cancer is the fourth most common malignancy in women and the precursor lesion is endometrial hyperplasia. HOXA10 is a transcription factor that plays key roles in endometrial functions such as the endowment of receptivity, embryo implantation, and trophoblast invasion. Herein, using testicular transgenesis, we developed transgenic mice that expressed a shRNA against HOXA10 and there was a nearly 70% reduction in the expression of HOXA10 in these animals. We observed that downregulation of HOXA10 led to the development of endometrial hyperplasia in the young animals (3 months), and as they aged (>1 year), most animals developed well-differentiated endometrial adenocarcinoma. In the endometrium of animals with reduced HOXA10, there was increased proliferation and elevated levels of ERα and ERβ. In parallel, there was increased expression of Wnt4 and β-Catenin, SOX9, and YAP1. We propose that chronic reduction in HOXA10 expression disrupts multiple pathways in the uterus that aids in the development of endometrial hyperplasia which progresses to endometrial cancer with age.

The host defence of insects includes a combination of cellular and humoral responses. The cellular arm of the insect innate immune system includes mechanisms that are directly mediated by haemocytes (e.g., phagocytosis, nodulation and encapsulation). In addition, melanization accompanying coagulation, clot formation and wound healing, nodulation and encapsulation processes leads to the formation of cytotoxic redox-cycling melanin precursors and reactive oxygen and nitrogen species. However, demarcation between cellular and humoral immune reactions as two distinct categories is not straightforward. This is because many humoral factors affect haemocyte functions and haemocytes themselves are an important source of many humoral molecules. There is also a considerable overlap between cellular and humoral immune functions that span from recognition of foreign intruders to clot formation. Here, we review these immune reactions starting with the cellular mechanisms that limit haemolymph loss and participate in wound healing and clot formation and advancing to cellular functions that are critical in restricting pathogen movement and replication. This information is important because it highlights that insect cellular immunity is controlled by a multilayered system, different components of which are activated by different pathogens or during the different stages of the infection.

Hox genes code for transcription factors and are evolutionarily conserved. They regulate a plethora of downstream targets to define the anterior-posterior (AP) body axis of a developing bilaterian embryo. Early work suggested a possible role of clustering and ordering of Hox to regulate their expression in a spatially restricted manner along the AP axis. However, the recent availability of many genome assemblies for different organisms uncovered several examples that defy this constraint. With recent advancements in genomics, the current review discusses the arrangement of Hox in various organisms. Further, we revisit their discovery and regulation in Drosophila melanogaster. We also review their regulation in different arthropods and vertebrates, with a significant focus on Hox expression in the crustacean Parahyale hawaiensis. It is noteworthy that subtle changes in the levels of Hox gene expression can contribute to the development of novel features in an organism. We, therefore, delve into the distinct regulation of these genes during primary axis formation, segment identity, and extra-embryonic roles such as in the formation of hair follicles or misregulation leading to cancer. Toward the end of each section, we emphasize the possibilities of several experiments involving various organisms, owing to the advancements in the field of genomics and CRISPR-based genome engineering. Overall, we present a holistic view of the functioning of Hox in the animal world.