Biochemical and Biophysical Research Communications
Long non-coding RNA UCA1 promotes lung cancer cell proliferation and migration via microRNA-193a/HMGB1 axis
Introduction
As one of the most common cancers, lung cancer has become a major public health problem worldwide. Lung cancer is one of the most leading causes of cancer mortality with an overall five-year survival rate of approximately 17%, and 1,6 million deaths in 2012 [1]. Even many types of therapies for lung cancer have been tried and achieved some achievements. There are still no significant improvements in patients' survival rate. Thus, we need more uniformly effective and complementary option in the treatment of lung cancer.
Recent decades, a growing number of long non-coding RNAs (lncRNAs) have been discovered. LncRNAs are a large family of evolutionarily conserved non-coding RNAs with length ranging from 200 nucleotides to 100,000 nucleotides [2]. lncRNA was identified to play key roles in various cellular processes, including chromatin dynamics, embryonic development, differentiation and carcinogenesis by affecting gene expression at various levels including transcription, RNA processing and transportation, and translation [[3], [4], [5], [6]]. Researches documented that the aberrantly expression of lncRNA could affect cell growth, migration, invasion and apoptosis in a variety of tumors [7,8]. However, the mechanisms of lncRNA acts in various types of cancer remain largely vague.
Human urothelial carcinoma associated 1 (UCA1), is a lncRNA which was initially discovered and dissected in bladder cancer [9]. Several reports documented the highly expressed UCA1 in a variety of tumors, including hepatocellular carcinomas, ovarian, colon, pancreatic, gastric, breast, renal as well as lung cancers [[10], [11], [12], [13]]. Researches reported UCA1 exerted an oncogenic role in tumor proliferation and metastasis, and served as a novel biomarker for diagnosis and prognosis of cancers [11,14]. In 2015, Wei Nie and colleagues demonstrated that UCA1 regulated the expression of ERBB4 via sponging micro RNA miR-193a-3p in non-small cell lung cancer [15]. However, the role of UCA1 in lung cancer and its underlying mechanism needs to be further investigation.
Until now, the detailed molecular mechanism by which lncRNA plays its role in lung cancer has not been elaborated. Recently, more and more researches documented the regulatory mechanism about ceRNAs hypothesis in variety of cancers. ceRNAs (competing endogenous RNAs) was defined as lncRNAs exerts as a molecular sponge to competitive adsorption of miRNA with mRNA and thereby leading to the inhibition of the activities of miRNAs and restoring the expression and activities of miRNA targets. Thus, any perturbation of ceRNA pathway might result in the pathologic processes in variety of cancers. Several reports demonstrated that miR-193a act as anti-tumor effect and down-regulated in cancers. Nie W and colleagues found that long non-coding RNA UCA1 functions as an oncogene by modulating ERBB4 expression by interacting with miR-193a and promote cell growth and metastasis in NSCLC. However, the ceRNAs in lung cancer development remains to be clarified.
In this study, we sought to dissect the role and mechanism of UCA1 in lung cancer. As shown in this study, we discovered the function and the mechanism of UCA1/miR-193a/HMGB1 pathway in the cell progress of lung cancer cells.
Section snippets
Cell culture
Cell lines H520, SKMES1 are maintained in Dulbecco's modified Eagle's medium (DMEM) as recommended by the American Type Culture Collection (ATCC). All media were supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin. All cell lines were cultured in a humidified atmosphere at 37 °C containing 5% CO2.
RNA interference and cell transfection
Gene-specific stealth RNAi oligonucleotides (siRNA) were designed and synthesized by GenePharma (Shanghai). The sequences of siRNAs were described as follow: siUCA1-1: 5′
Knockdown of UCA1 inhibited cell proliferation and migration in lung cancer cells
In order to identify the biological role of UCA1 in the development and progression of lung cancer, we firstly designed siRNAs specific to UCA1 and transfected them into SKMES-1 and H520 cells respectively and then employed qPCR analysis to detect the inhibition efficiency of these siRNAs. The results demonstrated that the three UCA1 siRNAs could effectively repress UCA1 expression (Fig. 1A). We then applied the CCK8 and transwell assay to detect whether the repression of UCA1 could affect cell
Discussion
In summary, our study demonstrated that reduced UCA1 expression inhibited the cell proliferation and migration in both SKMES-1 and H520 lung cancer cells. Further investigation demonstrated that UCA1 exerts its function via regulating the miR-193a and HMGB1 expression. Therefore, we proved the role of the UCA1 and the underlying mechanism in lung cancer cells.
Recent decades, hallmarks of cancers were elaborated and recognized. Hanahan and Weinberg summarized them as self-sufficiency in growth
Declaration of interest
The authors report no conflicts of interest.
Acknowledgements
This work was granted by the Guide Project of the Science and Technology Commission of Shanghai Mulicipality (grant 124119a8000).
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