Despite the fact that great advances have been made in the management of non-small cell lung cancer (NSCLC), the prognosis of advanced NSCLC remains very poor. HOX transcript antisense intergenic RNA (HOTAIR) has been identified as an oncogenic long noncoding RNA (lncRNA) that is involved in the progression of a variety of carcinomas and acts as a negative prognostic biomarker. Yet, little is known about the effect of HOTAIR in the hypoxic microenvironment of NSCLC. The expression and promoter activity of HOTAIR were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and luciferase reporter assay. The function of the hypoxia-inducible factor-1α (HIF-1α) binding site to hypoxia-responsive elements (HREs) in the HOTAIR promoter region was tested by luciferase reporter assay with nucleotide substitutions. The binding of HIF-1α to the HOTAIR promoter in vivo was confirmed by chromatin immunoprecipitation assay (CHIP) and electrophoretic mobility shift assay (EMSA). The effect of HIF-1α suppression by small interference RNA or YC-1 on HOTAIR expression was also determined. In the present study, we demonstrated that HOTAIR was upregulated by hypoxia in NSCLC cells. HOTAIR is a direct target of HIF-1α through interaction with putative HREs in the upstream region of HOTAIR in NSCLC cells. Furthermore, HIF-1α knockdown or inhibition could prevent HOTAIR upregulation under hypoxic conditions. Under hypoxic conditions, HOTAIR enhanced cancer cell proliferation, migration, and invasion. These data suggested that suppression of HOTAIR upon hypoxia of NSCLC could be a novel therapeutic strategy.

Involvement of the RGS17 oncogene in the promotion of non‐small‐cell lung cancer (NSCLC) has been reported, but the regulation mechanism in NSCLC remains unclear. MicroRNAs (miRNAs) negatively regulate gene expression, and their dysregulation has been implicated in tumorigenesis. To understand the role of miRNAs in Regulator of G Protein Signaling 17 (RGS17)‐induced NSCLC, we showed that miR‐203 was downregulated during tumorigenesis, and inhibited the proliferation and invasion of lung cancer cells. We then determined whether miR‐203 regulated NSCLC by targeting RGS17. To characterize the regulatory effect of miR‐203 on RGS17, we used lung cancer cell lines, A549 and Calu‐1, and the constructed miR‐203 and RGS17 overexpression vectors. The CCK8 kit was used to determine cell proliferation, and the Transwell® assay was used to measure cell invasion and migration. RT‐PCR, western blots, and immunofluorescence were used to analyze expression of miR‐203 and RGS17, and the luciferase reporter assay was used to examine the interaction between miR‐203 and RGS17. Nude mice were used to characterize in vivo tumor growth regulation. Expression of miR‐203 inhibited proliferation, invasion, and migration of lung cancer cell lines A549 and Calu‐1 by targeting RGS17. The regulatory effect of miR‐203 was inhibited after overexpression of RGS17. The luciferase reporter assay showed that miR‐203 downregulated RGS17 by direct integration into the 3′‐UTR of RGS17 mRNA. In vivo studies showed that expression of miR‐203 significantly inhibited growth of tumors. Taken together, the results suggested that expression of miR‐203 inhibited tumor growth and metastasis by targeting RGS17.

ObjectivesTo estimate the current prevalence of cardiovascular disease risk factors (CRFs) and renal disorders across serum uric acid (SUA) quartiles, and evaluate the relationships between SUA and CRFs and renal diseases in Shanghai population.Study designObservational, cross-sectional study.SettingData were obtained from the physical check-up of local residents at three hospitals in Shanghai.ParticipantsResidents were invited to take part in a physical check-up and provided informed consent. Exclusion criteria were diseases that resemble cancer, hepatic disease, and other coexisting illnesses including autoimmune kidney diseases and renal artery stenosis, individuals treated with xanthine oxidase inhibitors, and those with incomplete information. There are 26 768 individuals in our study.Primary and secondary outcome measuresHyperuricaemia was defined as SUA ≥7 mg/dL in men and ≥6 mg/dL in women or taking xanthine oxidase inhibitors. Subjects were divided into gender-specific quartiles. We estimate the prevalence of CRFs and renal disorders across SUA quartiles. The relationships between SUA and CRFs and renal disorders in both genders were evaluated using logistic regression analysis.ResultsThere was a significant increase in the prevalence of major CRFs and renal diseases across SUA quartiles in a separate analysis among men and women (all p trend <0.001). After multiple adjustment, hyperuricaemia positively correlated with obesity (male OR=3.165, p<0.001; female OR=3.776, p<0.001), hypertension (male OR=1.341, p<0.001; female OR=1.289, p=0.006), dyslipidaemia (male OR=2.490, p<0.001; female OR=3.614, p<0.001), chronic kidney disease (male OR=7.081, p<0.001; female OR=11.571, p<0.001) and nephrolithiasis (male OR=1.469, p<0.001; female OR=1.242, p=0.041), but negatively correlated with diabetes mellitus (male OR=0.206, p<0.001; female OR=0.524, p<0.001). There was a stronger association between hyperuricaemia and clustered CRFs as well as chronic kidney disease in women than in men.ConclusionsIn Shanghai population, concomitant with the elevated level of SUA, the prevalence of CRFs and renal diseases was rising. Hyperuricaemia was significantly associated with CRFs and renal disorders, especially in women.

A growing number of circular RNAs (circRNAs) have been identified and verified in several cancers. However, highly efficient therapeutic methods based on circRNAs in lung cancer remain largely unexplored. In the present study, we identified a novel circular RNA, hsa_circ_103820, based on Gene Expression Omnibus (GEO) data. Functionally, overexpression of hsa_circ_103820 showed significant inhibitory effects on the proliferation, migration and invasion of lung cancer cells, and knockdown of hsa_circ_103820 played promoting roles. Regarding the mechanism, we revealed that miR-200b-3p was a direct target of hsa_circ_103820 and that LATS2 and SOCS6 were the downstream target genes of miR-200b-3p. Therefore, we identified a novel potential tumor suppressive function of hsa_circ_103820 in lung cancer.