Abstract
B-Myb is a transcription factor that is overexpressed and plays an oncogenic role in several types of human cancers. However, its potential implication in lung cancer remains elusive. In the present study, we have for the first time investigated the expression profile of B-Myb and its functional impact in lung cancer. Expression analysis by quantificational real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry demonstrated that B-Myb expression is aberrantly overexpressed in non-small cell lung cancer (NSCLC), and positively correlated with pathologic grade and clinical stage of NSCLC. A gain-of-function study revealed that overexpression of B-Myb significantly increases lung cancer cell growth, colony formation, migration, and invasion. Conversely, a loss-of-function study showed that knockdown of B-Myb decreases cell growth, migration, and invasion. B-Myb overexpression also promoted tumor growth in vivo in a NSCLC xenograft nude mouse model. A molecular mechanistic study by RNA-sequencing (RNA-seq) analysis showed that B-Myb overexpression causes up-regulation of various downstream genes (e.g., COL11A1, COL6A1, FN1, MMP2, NID1, FLT4, INSR, and CCNA1) and activation of multiple critical pathways (e.g., extracellular signal-regulated kinases (ERK) and phosphorylated-protein kinase B (Akt) signaling pathways) involved in cell proliferation, tumorigenesis, and metastasis. Collectively, our results indicate a tumor-promoting role for B-Myb in NSCLC and thus imply its potential as a target for the diagnosis and/or treatment of NSCLC.
Highlights
Lung cancer is the most common incident cancer and remains the leading cause of cancer-related deaths in China and worldwide [1,2,3]
The quantificational real-time polymerase chain reaction analysis on a panel of lung cancer complementary DNA arrays including 40 patients with lung cancer and seven healthy controls demonstrated that B-Myb was significantly up-regulated at the mRNA level in lung cancer samples compared with normal lung tissues (p = 0.002; Figure 1A)
Nakajima et al reported firstly that B-Myb is overexpressed in primary hepatocellular carcinoma (HCC) [12]
Summary
Lung cancer is the most common incident cancer and remains the leading cause of cancer-related deaths in China and worldwide [1,2,3]. The two major forms of lung cancer are non-small cell lung cancer (NSCLC, about 85% of all lung cancers) and small-cell lung cancer (SCLC, about 15%). NSCLC is further classified into three major histologic subtypes: squamous-cell carcinoma (SQCC), adenocarcinoma (ADC), and large-cell lung cancer. B-Myb stimulates transcription of genes that promote entry into the S- and M-phases of cell cycle [17]. B-Myb has been shown to be overexpressed in a broad range of human cancers, such as breast cancer [18], hepatocellular carcinoma [10], lung cancer [19], colon cancer [20], neuroblastoma [21], and T-cell lymphomas [22]. The expression profile of B-Myb and its potential functional impact in lung cancer have not been investigated and remain elusive
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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
