ObjectiveTo study value of long noncoding RNA H19 and HOTTIP in plasma in predicting efficacy of neoadjuvant chemotherapy (NAC) for resectable locally advanced gastric cancer. MethodsForty patients with T3–4aN+M0 gastric cancer and 40 patients with benign gastric diseases treated in the Yantai Yuhuangding Hospital Affiliated to Qingdao University from August 2020 to May 2021 were prospectively included. The expressions of H19 and HOTTIP in the plasma of gastric cancer and benign gastric diseases patients without any treatment after admission were detected before treatment (CAPEOX regimen was used in the patients with gastric cancer), then which were detected after 2 NAC courses for patients with gastric cancer. Meanwhile, some clinical items were detected and the efficacy of NAC was evaluated. The complete remission (CR) and partial remission (PR) were classified as objective remission, CR, PR, and disease stability were classified as disease control. The expressions of H19 and HOTTIP between the different patients were compared and the receiver operating characteristic (ROC) curve was used to evaluate their values in the diagnosis of resectable locally advanced gastric cancer. ResultsThere were 13 cases of T downstaging and 27 cases of T non-downstaging and 25 cases of objective remission and 35 disease control after NAC. The median relative expression levels of H19 and HOTTIP before NAC in the patients with gastric cancer were higher than those in the patients with benign gastric diseases (H19: 1.42 versus 0.98, Z=–3.835, P<0.001; HOTTIP: 2.15 versus 1.04, Z=–5.062, P<0.001), and which were in the patients with T downstaging and disease control were lower than those in the patients with T non-downstaging and 5 cases of disease progression (For T staging, H19: 1.12 versus 1.54, Z=–2.960, P=0.002; HOTTIP: 1.49 versus 2.30, Z=–2.310, P=0.019. For efficacy of NAC, H19: 1.39 versus 2.48, Z=–3.211, P<0.001; HOTTIP: 1.96 versus 3.25, Z=–2.393, P=0.014). The median relative expressions of H19 and HOTTIP after NAC were lower than those before NAC in the patients with gastric cancer (H19: 1.12 versus 1.42, Z=–3.965, P<0.001; HOTTIP: 1.30 versus 2.15, Z=–4.839, P<0.001). There were no significant differences in the changes of H19 and HOTTIP before and after NAC between the patients with T downstaging and T non-downstaging, and between disease control and disease progression (P>0.05). The areas of ROC curve of H19, HOTTIP, and combination of H19 and HOTTIP in diagnosis of resectable locally advanced gastric cancer were higher than 0.7. ConclusionsLncRNA H19 and HOTTIP might be potential tumor markers in gastric cancer, and their diagnostic values for resectable locally advanced gastric cancer are higher. Gastric cancer patients with low expressions of H19 and HOTTIP in plasma might be more sensitive to NAC.
Objective To explore the effect of long non-coding RNA H19 (lncRNA H19) on chronic heart failure (CHF) rats and its possible mechanism. Methods CHF (SD male rats, with a weight of 300±10 g, 10 weeks old) rat model was established by abdominal aortic coarctation. The 84 rats successfully modeled were randomly divided into a model group, a si-NC group [transfected lncRNA H19 small interfering RNA (siRNA) negative control], a si-H19 group (transfected lncRNA H19 siRNA), a si-miR-NC group [transfected microRNA-214 (miR-214) siRNA negative control], a si-miR-214 group (transfected miR-214 siRNA), a si-H19+si-miR-NC group (co-transfected lncRNA H19 siRNA and miR-214 siRNA negative control), and a si-H19+si-miR-214 group (co-transfected lncRNA H19 siRNA and miR-214 siRNA), 12 rats in each group. Another 12 rats were set up in a sham operation group (rats were only threaded without ligation, and the other operations were the same as the model group). After 4 weeks of intervention, the cardiac function, serum myocardial injury markers, heart failure markers, inflammatory related factors, apoptosis related factors and myocardial histopathological changes were compared. The expressions of lncRNA H19 and miR-214 in myocardial tissue were detected by real-time fluorescence quantitative PCR, and the targeting relationship between lncRNA H19 and miR-214 was detected by double luciferase reporter gene. Results Compared with those in the sham operation group, the myocardium of rats in the model group was severely damaged and a large number of inflammatory cells infiltrated; the lncRNA H19, cardiac function indexes (left ventricular end systolic diameter, left ventricular end diastolic diameter), serum myocardial injury markers (creatine kinase MB, cardiac troponin I), heart failure markers (brain natriuretic peptide, N-terminal pro brain natriuretic peptide), inflammatory related factors (interleukin-1β, interleukin-18, tumor necrosis factor-α, interleukin-6), cardiomyocyte apoptosis rate, apoptosis related proteins [B lymphocytoma-2 (Bcl-2), Bcl-2 related X protein (Bax), cysteinyl aspartate specific proteinase-1 (Caspase-1)] in the myocardial tissue of the model group were significantly increased (P<0.05); miR-214 of myocardial tissue, cardiac function indexes (left ventricular ejection fraction, left ventricular fractional shortening) and Bcl-2/Bax ratio were significantly decreased (P<0.05). Compared with the model group, silencing lncRNA H19 could significantly improve the cardiac function and the changes of the above indexes in CHF rats, and reduce myocardial injury (P<0.05); down-regulation of miR-214 could significantly reverse the protective effect of si-H19 on myocardial injury in CHF rats (P<0.05). Conclusion Silencing lncRNA H19 can up-regulate the expression of miR-214, inhibit the expression of Caspase-1, inhibit the apoptosis and inflammatory reaction of cardiomyocytes, and alleviate myocardial injury in rats with CHF.