Purpose: Non-small cell lung cancer (NSCLC) is the largest type of lung cancer (LC) with a higher mortality rate. Circular RNAs (circRNAs) have been shown to play an important role in cancer progression. Therefore, this study was to explore the function of hsa_circ_0043265 in NSCLC. Methods: The expression levels of hsa_circ_0043265, microRNA-25-3p (miR-25-3p) and forkhead box P2 (FOXP2) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Ribonuclease R (RNase R) and Actinomycin D (ActD) were used to verify the authenticity and stability of hsa_circ_0043265. Cell counting kit-8 (CCK-8), flow cytometry and transwell assays were used to evaluate the abilities of proliferation, apoptosis, migration and invasion of NSCLC cells. Also, Western blot (WB) analysis was performed to assess the levels of apoptosis, epithelial-mesenchymal transition (EMT) and proliferationrelated proteins and FOXP2 protein. RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were used to verify the interaction between miR-25-3p and hsa_circ_0043265 or FOXP2. Besides, mice xenograft models were constructed to confirm the effect of hsa_circ_0043265 on NSCLC tumor growth in vivo. Results: Hsa_circ_0043265 was lowly expressed in NSCLC tissues and cells, and its overexpression inhibited the proliferation, migration, invasion and EMT process, while improved the apoptosis of NSCLC cells. MiR-25-3p could be sponged by hsa_circ_0043265, and its overexpression could invert the suppression effect of overexpressed-hsa _circ_0043265 on NSCLC progression. Moreover, FOXP2 was a target of miR-25-3p, and its silencing also could reverse the inhibition effect of overexpressed-hsa_circ_0043265 on NSCLC progression. In addition, hsa_circ_0043265 overexpression reduced the tumor growth of NSCLC in vivo. Conclusion: Hsa_circ_0043265 could sponge miR-25-3p to improve FOXP2 expression, thereby inhibiting NSCLC progression. This study showed that hsa_circ_0043265 could be a potential biomarker for early diagnosis of NSCLC.

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Background: Long non-coding RNA colorectal neoplasia differentially expressed (lncRNA CRNDE) and microRNA-126-5p (miR-126-5p) were reported to be related to the development of colorectal carcinoma (CRC). However, the detailed mechanism of CRNDE and miR-126-5p is not fully understood. The purpose of this research was to explore their roles and molecular mechanism in CRC. Methods: Quantitative real-time polymerase chain reaction was performed to detect the transcription levels of genes. Paclitaxel (PTX) was used to analyze cell drug resistance. 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and flow cytometry analysis were employed to assess cell proliferation and apoptosis, respectively. Furthermore, cell migratory and invasive abilities were measured using transwell assay. The interaction between miR-126-5p and CRNDE or ATPase family AAA domain-containing protein 2 (ATAD2) was predicted by online tool starbase and then confirmed using the dualluciferase reporter assay. Besides, Western blot assay was carried out to detect the levels of proteins. Results: CRNDE and ATAD2 expressions were upregulated and miR-126-5p expression was downregulated in CRC tissues and cells. CRNDE depletion repressed PTX resistance and the growth of CRC cells. Interestingly, we found that miR-126-5p was a target gene of CRNDE, and miR-126-5p directly targeted ATAD2. Furthermore, CRNDE affected CRC cell progression via modulation of miR-126-5p/ATAD2 axis in CRC cells. Conclusion: Our data suggested that CRNDE regulated CRC cell development and PTX resistance by modulating miR-126-5p/ATAD2 axis, providing the theoretical basis for the treatment of CRC patients.

Gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in central nervous system, has yet been found to widely exist in tumor tissues to regulate tumor cells growth. However, the function of GABA on inducing tumor cells apoptosis and the potential mechanism are still unclear. In order to detect whether GABA via GABAB receptor GABABR1 would activate c-Jun N-terminal kinases (JNKs) to promote tumor cells apoptosis, co-immunoprecipitation assay was used to investigate the association of β-arrestins with GABABR1 and JNKs in the different four cancer cell lines. Our observation demonstrated that β-arrestins, in addition to their role in G protein-coupled receptors desensitization, had an additional function as adapter proteins to recruit JNKs to GABABR1, thereby conferring distinct enzymatic activities upon the receptor, which may trigger JNKs signal pathway involved in the regulation of cellular growth. Activated JNKs subsequently phosphorylated downstream c-Jun to transcribe a wide variety of pro-apoptotic genes. Additionally, GABA up-regulated the ratio of pro-apoptotic protein Bax to anti-apoptotic protein Bcl-2, and thus facilitated caspase-3 cleavage, leading to tumor cells apoptosis in a mitochondrial-dependent pathway. In contrast, GABABR antagonist CGP35348 reversed GABA-induced JNKs phosphorylation and its downstream proteins activation, which consequently restrained tumor cells apoptosis. Taken together, our study suggested that GABA via its receptor GABABR1 recruited β-arrestins to facilitate the activation of JNKs cascade, resulting in tumor cells growth inhibition.

Asian Pac J Cancer Prev, 15 (2), 1041-1046 IntroductionAs one of the most common types of cancer, breast cancer represents the most prevalent and lethal malignancy among female. Its incidence in China has gradually increased accompanied with the changes in people's lifestyle (Wang et al., 2013). Despite developments in surgery and the increased number of drugs for radio-and chemotherapy, post-operative morbidity and other health problems significantly reduced the life quality of patients (Li et al., 2013). Thus, a better understanding of the molecular mechanism that drives breast cancer growth and invasion is required to promote development of more effective therapies for breast cancer patients.GABA, also known as γ-aminobutyric acid, was originally identified as a principal inhibitory neurotransmitter which widely distributes in the adult mammalian brain (Watanabe et al., 2002). There are three different types of GABA receptors including ionotropic receptor families GABA A R and GABA C R. GABA A R is commonly used as a drug target in clinical practice, while GABA C R is found exclusively in the retina. As G protein-coupled receptors (GPCR), GABA B receptors are seven trans-membrane receptors which are coupled to G-proteins to counteract the activity of betaadrenoreceptors (β-ARs) in the central nervous system via GABA B receptor-mediated inhibition of adenylyl cyclase (Chebib et al., 1999;Gladkevich et al., 2006