<p>Long Noncoding RNA DIO3OS Hinders Cell Malignant Behaviors of Hepatocellular Carcinoma Cells Through the microRNA-328/Hhip Axis</p>
Authors: Lina Song
Yanshuo Ye
Zhanpeng Wang
Wei Li
Journal: Cancer Management and Research (2020)
Discipline: CLINICAL MEDICINE
Keywords: DIO3OS; Hhip; competing endogenous RNA; hedgehog signaling pathway; microRNA-328
Affiliations: Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun 130000, People's Republic of China., Department of Laboratory Medicine Center, China-Japan Union Hospital of Jilin University, Changchun 130000, People's Republic of China.

Abstract:  Background: The decline of a long non-coding RNA (lncRNA) DIO3OS was implicated in a plethora of cancers, while the relevance in hepatocellular carcinoma (HCC) has not been mentioned. Accordingly, we set to determine the functional role of DIO3OS and the molecular mechanism in HCC progression. Materials and methods: The differentially expressed lncRNAs, mRNAs, and microRNAs (miRNAs) were obtained through the datasets GSE101728 and GES57555. Afterwards, DIO3OS was enhanced in HCC cells to examine the behavior changes. Subcellular localization of DIO3OS was determined through website prediction and experimental validation. The expression of Hedgehog (Hh) signaling pathway-related genes was detected. The effects of DIO3OS overexpression on tumor growth were evaluated as well. Results: DIO3OS was lower in HCC tissues and cells, while upregulation of DIO3OS repressed malignant biological behavior both in vitro and in vivo. DIO3OS, localized in the cytoplasm, inhibited the occurrence of HCC by disrupting the Hh pathway by sponging miR-328 to mediate ÔªøHh interacting protein (Hhip). Conclusion: All in all, the obtained data suggested that DIO3OS interacted with Hhip-dependent Hh signaling pathway to inhibit HCC progression through binding to miR-328, which may be a potent therapeutic target for HCC. 

Retracted: No

PubPeer comments:
 ###  Slow MOTION : Methylnaltrexone ineffective for constipation in intensive care Constipation occurs in up to 70% of patients receiving intensive care and is associated with increased mortality. Opioids in the context of analgosedation are a cause of this multifactorial event. Whether the preventive use of laxatives leads to an improvement is still unclear.[1][2] Methylnaltrexone is a peripherally active u03bc receptor antagonist, approved in the therapy of laxant-refractory opioid-induced constipation, which has shown efficacy in the palliative setting.[3] In the British, non-industry-funded, double-blind, multi-center, randomized controlled MOTION study, the efficacy of methylnaltrexone vs. placebo in the treatment of constipation in intensive care units has now been investigated. The study included 84 machine-ventilated, analgosedated patients who had not had a bowel movement for at least 48 hours despite the use of laxatives. Patients who had not passed stool 72 hours after the start of the study medication received rescue therapy with laxatives. For the primary endpoint, defined as the passage of a significant amount of stool ( 100 mL), there was no significant difference between methylnaltrexone and placebo (HR 1.42; 95% KI 0.82-2.46; p = 0.22). In days 4-28 of the follow-up period, the methylnaltrexone group not only had a significantly lower number of daily bowel movements (p = 0.01), but also significantly more deaths (10 vs. 2; p = 0.007). An investigation of the deaths involving the authorities did not reveal any indication of a link with the administration of the study medication, but could not be explained in post-hoc analyses by differences in baseline characteristics between the treatment groups. The width of the confidence interval to the primary endpoint as well as the unclear discrepancy in mortality between the groups indicate that the study lacked sufficient power. However, the development towards more differentiated, less intensive sedation protocols as well as an earlier start of enteral nutrition in critically ill patients could in future reduce the importance of opioid antagonists in the treatment of constipation in intensive care patients. --- [1]: [Hay et al.: Constipation, diarrhea, and prophylactic laxative bowel regimens in the critically ill: A systematic review and meta-analysis. In: Journal of Critical Care. Band: 52, 2019] [2]: [Oczkowski et al.: The Use of Bowel Protocols in Critically Ill Adult Patients. In: Critical Care Medicine. Band: 45, Nummer: 7, 2017] [3]: [Candy B, Jones L, Vickerstaff V, Larkin PJ, Stone P: Mu-opioid antagonists for opioid-induced bowel dysfunction in people with cancer and people receiving palliative care.. In: The Cochrane database of systematic reviews. Band: 6, 2018] ,