BaCKgRoUND aND aIMS: Long noncoding RNAs (lncRNAs) are involved in almost every stage of tumor initiation and progression. Here, we have identified an antisense lncRNA, LINC00624, that arises from the antisense strand of chromo-domain-helicase-DNA-binding protein 1-like (CHD1L), located on chr1q21.1, with significant copy number gain and transcriptional activation of CHD1L and B-cell CLL/lymphoma 9 protein (BCL9), in hepatocellular carcinoma (HCC). appRoaCH aND ReSUltS: Overexpression of LINC00624 enhances tumor growth and metastasis in vitro and in vivo. Mechanistically, higher levels of LINC00624 strengthen the interaction between histone deacetylase 6 (HDAC6) and tripartite motif containing 28 (TRIM28), which accelerates HDAC6 ubiquitination and degradation. Moreover, LINC00624 binds to the RBCC domain of TRIM28, inhibits trimer formation, and weakens the interaction between TRIM28 and zinc finger protein 354C (ZNF354C). Thus, LINC00624 overexpression disrupts the formation of the HDAC6-TRIM28-ZNF354C transcriptional corepressor complex, resulting in the dissociation of the complex from the promoter of CHD1L and BCL9, thereby removing transcription inhibition.
CoNClUSIoNS:Our findings suggest that LINC00624 acts as a molecular decoy that sequesters the HDAC6-TRIM28-ZNF354C transcriptional corepressor complex away from the specific genomic loci, and that it can potentially be a therapeutic target in HCC. (Hepatology 2021;73:1764-1782).H epatocellular carcinoma (HCC) is the fourth-leading cause of cancer-related deaths worldwide and correlates with poor prognosis, with a 5-year survival of 18%. (1) After standard systemic therapy, the median overall survival is 6-9 months for all stages of untreated HCC, based on the Barcelona Clinic Liver Cancer staging system. (2,3) Patients with HCC accumulate somatic mutations and chromosomal aberrations, which results in patients at the same clinical stage with different molecular subtypes. (1,4) This leads to an uneven treatment effect.
PurposeTo explore the treatments and short-term effects of different types of adult Hirschsprung’s disease.Methods89 patients treated in Shanghai Changhai Hospital were retrospectively analyzed. According to the patient’s medical history, clinical manifestations, auxiliary examination and postoperative pathological results, the patients were divided into adult congenital megacolon, adult idiopathic megacolon, ganglion cell deficiency (types I and II), toxic megacolon and iatrogenic megacolon, The Treatment methods and short-term prognosis of patients in each group were summarized.Results41 cases of Hirschsprung’s disease in adults and low anterior resection or pull-out low anterior resection was performed, and 35 patients with idiopathic Megacolon were treated with one-stage subtotal colon resection under the condition of adequate preoperative preparation. Some patients admitted for emergency intestinal obstruction received conservative treatment first or underwent elective surgery after colonoscopic decompression was improved; two patients with ganglion cell deficiency subtotal colectomy were performed to remove the dilated proximal bowel segment and the narrow distal bowel segment; three patients with toxic Hirschsprung’s disease underwent colostomy in mild cases, while subtotal colorectal resection was required in severe cases; Iatrogenic megacolon was diagnosed in eight cases and the optimum operation should be selected according to the specific conditions of patients.ConclusionAdult Hirschsprung’s diseases were divided into adult congenital hirschsprung’s disease, idiopathic Hirschsprung’s disease, ganglion cell deficiency, toxic hirschsprung’s disease, and iatrogenic Hirschsprung’s disease. Different types of surgical treatments for Hirschsprung’s disease in adults should be selected according to the specific diagnosis. All patients with adult Hirschsprung’s diseases have good short-term outcomes after surgical treatment.
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This article is linked to Rivera–Andrade et al papers. To view these articles, visit https://doi.org/10.1111/apt.16948 and https://doi.org/10.1111/apt.17059
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