Abstract
Homeobox (HOX) genes encode a family of transcription factors, which play crucial roles in numerous processes, and their dysregulation is involved in the carcinogenesis of many human cancers. In the present study, we investigated the roles of HOXC8 in non-small cell lung cancer (NSCLC). We showed that HOXC8 was upregulated in clinical NSCLC specimens compared to normal lung tissues, and the high expression of HOXC8 correlated with tumor node metastasis (TNM) stage, tumor status, lymph nodal status and poor relapse-free survival for lung cancer patients. Functionally, HOXC8 expression significantly promoted the proliferation, anchorage-independent growth and migration of NSCLC, and HOXC8 functioned as a transcription activator to induce the expression of TGFβ1, leading to an increase in the proliferation, anchorage-independent growth and migration of NSCLC. Furthermore, we demonstrated that HOXC8 expression was associated with chemoresistance and anti-apoptosis in NSCLC, suggesting that HOXC8 is a promising therapeutic target for chemosensitization of NSCLC to cisplatin. Altogether, our study defined a critical role of HOXC8 in promoting transcription of TGFβ1 and NSCLC tumorigenesis.
Highlights
Lung cancer is the leading cause of cancer deaths, accounting for more than one-quarter of cancer-related deaths worldwide[1]
HOXC8 expression is up-regulated in Non-small cell lung cancer (NSCLC) Previous studies indicate that HOXC8 plays an important role in multiple cancer progression, little is known about HOXC8 roles in lung cancer[13,20,21,22,23]
HOXC8 regulates TGFβ1 transcription To test whether HOXC8 directly regulates these genes transcription, we carried out chromatin immunopreciption (ChIP) to investigate whether HOXC8 binds to the promoter of these genes, and we found that HOXC8 bound to the promoter of TGFβ1 in A549 and NCI-H460 cells
Summary
Lung cancer is the leading cause of cancer deaths, accounting for more than one-quarter of cancer-related deaths worldwide[1]. Non-small cell lung cancer (NSCLC), which includes lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and large cell carcinoma, accounts for >80% of all lung cancers[2]. It is important to identify the molecular mechanisms underlined in the regulation of lung cancer cell aggressiveness. The homeobox (HOX) genes constitute a family of transcription factors that participate in a number of physiological processes, including embryonic development, cell proliferation and differentiation, etc[4]. Numerous evidences show that HOX genes are deregulated in multiple cancers such as prostate cancer, pancreatic cancer, breast cancer and lung cancer, in which deregulation of HOX genes can promote or repress cancer processes[5,6,7,8]. HOXB7 expression is significantly upregulated in colorectal cancer, and expression of HOXB7 promotes the aggressiveness of cancer cells[10]. HOXD8 was found to be downregulated in colorectal cancer and functioned as a
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
