Paralogous HOX13 Genes in Human Cancers

Abstract

Hox genes (HOX in humans), an evolutionary preserved gene family, are key determinants of embryonic development and cell memory gene program. Hox genes are organized in four clusters on four chromosomal loci aligned in 13 paralogous groups based on sequence homology (Hox gene network). During development Hox genes are transcribed, according to the rule of “spatio-temporal collinearity”, with early regulators of anterior body regions located at the 3’ end of each Hox cluster and the later regulators of posterior body regions placed at the distal 5’ end. The onset of 3’ Hox gene activation is determined by Wingless-type MMTV integration site family (Wnt) signaling, whereas 5’ Hox activation is due to paralogous group 13 genes, which act as posterior-inhibitors of more anterior Hox proteins (posterior prevalence). Deregulation of HOX genes is associated with developmental abnormalities and different human diseases. Paralogous HOX13 genes (HOX A13, HOX B13, HOX C13 and HOX D13) also play a relevant role in tumor development and progression. In this review, we will discuss the role of paralogous HOX13 genes regarding their regulatory mechanisms during carcinogenesis and tumor progression and their use as biomarkers for cancer diagnosis and treatment.

Functional Interaction among lncRNA HOTAIR and MicroRNAs in Cancer and Other Human Diseases

“…HOTAIR is not expressed in the early stage of zygotes [ 72 ] yet its activity is associated with the early stages of embryogenesis [ 73 ]. It contributes to the development of the lumbosacral region [ 25 ] skin and uro-genital system due to its ability to modulate the expression of some genes of the HOX gene network [ 74 ]. HOTAIR can also be involved in osteogenesis, modulating the expression of two osteogenic-related genes, ALPL and BMP2 [ 75 ].…”

Germline HOXB13 mutation p.G84E do not confer an increased bladder or kidney cancer risk in polish population

“…Some studies have confirmed that mutation in the HOXB13 gene was associated with early-onset prostate cancer men, cases with significantly elevated PSA and family history of prostate cancer [ 18 , 26 – 28 ]. Additionally, abnormal expression of HOXB13 has been detected in the development of leukemia, non-Hodkin’s Lymphoma, oral squamous cell carcinoma, glioma, colon, stomach and genitourinary cancers [ 17 , 29 – 36 ]. Ovarian, cervical and endometrial cancers overexpress HOXB13 [ 29 , 37 ].…”

“…Additionally, abnormal expression of HOXB13 has been detected in the development of leukemia, non-Hodkin’s Lymphoma, oral squamous cell carcinoma, glioma, colon, stomach and genitourinary cancers [ 17 , 29 – 36 ]. Ovarian, cervical and endometrial cancers overexpress HOXB13 [ 29 , 37 ]. Moreover a link with melanoma cancer has been suggested and it predicts breast cancer recurrence and response to tamoxifen treatment [ 23 , 37 – 39 ].…”

Aberrant Expression of Long Non Coding RNA HOTAIR and De-Regulation of the Paralogous 13 HOX Genes Are Strongly Associated with Aggressive Behavior of Gastro-Entero-Pancreatic Neuroendocrine Tumors

“…Although the entire HOX network plays a central role in cancer development and progression, the most posterior genes of the network are crucial in modulating these processes, in cooperation with co-localizing lncRNAs [24].…”