Roles of Mir-144-ZFX Pathway in Growth Regulation of Non-Small-Cell Lung Cancer

Abstract

BackgroundLung cancer is the leading cause of cancer-related death worldwide. Non-small cell lung carcinoma (NSCLC) accounts for most of the lung cancer cases and the prognosis of this disease remains poor despite decades of intensive investigation. Thus new insights into underlying mechanisms by which NSCLC develops are avidly needed as the basis for development of new lines of therapeutic strategies. The past decade has witnessed a growing interest on the regulatory roles of micro RNAs on various categories of malignancies. Related data has been well documented in carcinogenesis and pathophysiology of a variety of malignancies. Even so, there is a relative lack of data on roles of mir-144 in tumor biology and there has been no report showing the involvement of mir-144 in NSCLC development.Methods/Principal FindingFrom human NSCLC tumor tissue samples and cell culture samples, we found that the expression of mir-144 is associated with malignant phenotype of NSCLC. Further investigations showed that ectopic mir-144 expression dramatically inhibits NSCLC tumor cell growth and induces apoptosis as manifested by elevated apoptotic protein markers and flowcytometry change. Moreover, we also found that ZFX protein expression is also associated with malignant phenotype of NSCLC and knockdown of ZFX protein results in a similar effect as of ectopic mir-144 expression. Finally, we found that ZFX expression is highly adjustable upon presence of mir-144 and ectopic expression of ZFX dramatically dampens mir-144 action of tumor inhibition.ConclusionsOur results for the first time showed mir-144-ZFX pathway is involved in the development of NSCLC, which sheds a light for further investigations on underlying mechanisms toward better understanding and management of NSCLC.

miR‑144 suppresses proliferation and induces apoptosis of osteosarcoma cells via direct regulation of mTOR expression

“…Results of the present study are consistent with the results of previous studies on liver cancer and non-small cell lung cancer (34,35). It is generally considered that miR-144 is able to function as a suppressor gene of tumor proliferation and affect the prognosis of patients with osteosarcoma (36,37).…”

Overexpression of ZFX and its involvement in squamous cell carcinoma of the tongue

“…ZFX overexpression has been observed in variant types of cancer including human laryngeal SCC (LSCC) (12), prostate (13) and gastric cancer (14-16), human gliomas (17,18), non-small cell lung cancer (NSCLC) (19) and breast cancer (20). Consistent with these studies, here we showed that ZFX, a protein involved in survival and self-renewal of embryonic stem cells and implicated in the development of multiple types of cancer, was overexpressed in the tongue SCC samples.…”

A Critical Role of miR-144 in Diffuse Large B-cell Lymphoma Proliferation and Invasion

“…miR-144 was originally identified as an erythroid-specific miRNA required for the survival and maturation of erythroid lineage (14,15). Ample studies have also revealed important roles for miR-144 in tumorigenesis and cancer treatment (16). In different types of cancers, downregulation of miR-144 has been observed, such as osteosarcoma and mesothelioma, indicating that miR-144 may be a potential tumor suppressor (17,18).…”