With increasing mortality rates, lung carcinoma has already become the leading cause of cancer mortality in the world . Many genes are subjected to post-transcriptional regulation via control of the rate of mRNA turnover for transcripts bearing destabilizing cis-elements . Among the very few regulatory factors identified thus far, CELF1 regulates post-transcriptional gene expression by facilitating alternative splicing, translation , and mRNA degradation, and it functions by binding directly to RNA . Rattenbacher et al. identified the CELF1 gene and its target proteins as a critical posttranscriptional regulatory network that may play a role in the development of cancer . In addition to reports of involvement in breast cancer and leukemia development, the CELF1 gene may also play a significant role in tumorigenesis and the deterioration of certain tumors , which is also confirmed by the results in our present study.
Timchenko et al. first identified CELF1 function in the regulation of translation of C/EBP beta isoforms . Subsequent research demonstrated that members of this protein family regulate pre-mRNA alternative splicing and may also be involved in mRNA editing and translation . The CELF1 gene may play a role in myotonic dystrophy type 1 (DM1) via interactions with the dystrophia myotonica-protein kinase (DMPK) gene . A previous report identified a correlation between the expression of CELF1 and human lung cancer . However, the cellular mechanism underlying how the CELF1 gene causes this phenomenon has not been clarified. Together these findings implicate possible involvement of the CELF1 gene in cell growth. So far there is no literature reporting the biological function of CELF1 gene in lung cancer cell. We speculate that CELF1 may also play an important role in lung cancer proliferation.
Our research primarily focused on the effect of CELF1 knockdown on the viability of lung cancer cells. As shown in the results, the expression of CELF1 was higher in human lung cancer tissues compared with normal tissues. Moreover, A549 and H1299 lung cancer cells also exhibited CELF1 expression in mRNA and protein level. Lentiviral-mediated delivery of CELF1 silencing siRNA significantly inhibited these upregulated levels of CELF1 expression, demonstrating that the CELF1 knockdown method was successful. Further in vivo studies should be performed to confirm the use of this siRNA method as a potential therapeutic tool.
Interestingly, upon knockdown of CELF1, the survival rates and colony forming ability of lung cancer cells were markedly reduced, indicating pivotal roles of CELF1 in the survival of lung cancer cells. Reports in the literature have suggested that upregulation of CELF1 increased the turnover of oncogenes related to the proliferation of lung cancer cells [7, 9, 18]. Hence, in the absence of CELF1, the turnover of possible oncogenes could presumably decrease, consistent with the cancer cells showing decreased capacity of proliferation and colony formation. Our study showed that CELF1 is overexpressed in lung cancer tissue on RNA level compared with the normal lung tissue and tumor grades had relationship with CELF1 expression level, which is line with the hypothesis mentioned above.
From these results, we can conclude that CELF1 can affect the growth of lung cancer cells and plays an important role in the tumor development process. Further research on the molecular mechanisms of the CELF1 gene is required, particularly in identifying CELF1-interacting proteins, elucidating the molecular mechanisms underlying its biological effects, and determining whether it plays a guiding role in the treatment of lung cancer.