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Rationale : Post-translational modifications have emerged as vital players in alterations to tumor metabolism, including amino acid metabolic reprogramming. Jumonji domain-containing protein 2B (JMJD2B) enhances colorectal cancer (CRC) cell survival upon glucose deficiency. In the present study, we hypothesized that JMJD2B affects tumor cell amino acid metabolism in CRC and consequently promotes survival of CRC cells upon glucose deprivation. Methods : Non-target metabolic profiling was used to evaluate the roles of JMJD2B in CRC cell metabolism under glucose starvation. The roles of amino acid alterations induced by JMJD2B on CRC cell survival were determined by cell viability, immunoblotting, and clonogenic assays, and flow cytometry. The underlying mechanisms by which JMJD2B affected CRC cell metabolism were assessed using immunofluorescence staining, chromatin immunoprecipitation assays, electron microscopy in CRC cell lines, and using xenograft models. The correlation between JMJD2B and LC3B expression in human CRC specimens was assessed using immunohistochemistry. Results : Profound metabolic reprogramming was detected in JMJD2B knockdown CRC cells under glucose deficiency, especially those involving amino acid metabolites. Silencing of JMJD2B reduced the levels of certain amino acids that were induced by glucose deficiency. Among these amino acids, asparagine (Asn), phenylalanine (Phe), and histidine (His) promoted CRC cell survival under glucose starvation when JMJD2B was knocked down. Mechanistically, downregulation of JMJD2B inhibited autophagy in CRC cells through epigenetic regulation of microtubule associated protein 1 light chain 3 beta (LC3B), and subsequently decreased intracellular amino acid (Asn, Phe, His) levels under glucose deprivation, thus suppressing the survival of CRC cells. Using a nude mouse xenograft model, we verified that inhibiting JMJD2B could decrease the levels of amino acids (Asn, Phe, His). In addition, the inhibitory effects of JMJD2B -knockdown on tumor growth and amino acids level were rescued by overexpression of LC3B . Furthermore, we observed that the high expression of LC3B was more likely detected in tissuses with high expression of JMJD2B ( P < 0.001) in 60 human CRC tissues. Conclusion : These results indicated that JMJD2B sustained the intracellular amino acids derived from autophagy in CRC cells upon glucose deficiency, partly through epigenetic regulation of LC3B , thus driving the malignancy of CRC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Colon Cancer-Associated Transcript 2 (CCAT2) has been demonstrated associated with clinical outcomes in various tumors. However, the results from each study were unfortunately insufficient and not completely consistent. Therefore, we conduct a systematic meta-analysis to evaluate the value for a feasible biomarker for metastasis and prognosis. Methods: A meta-analysis was performed using data obtained through a systematic search of PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Wanfang database and VIP database. The pooled odds ratio (OR) and hazard ratio (HR) with 95% Confidence interval (CI ) using random-effect were used to identify the relationship of CCAT2 with clinical outcome of cancer patients. Subgroup analysis and sensitivity analysis were performed. Results: A total of 867 patients from eight studies were finally included. Patients with high CCAT2 expression underwent an increased risk of lymph node metastasis (LNM) (OR=3.09, 95% CI: 1.53-6.26) and distant metastasis (DM) (OR=7.70, 95% CI: 3.26-18.17). CCAT2 was also significantly correlated with overall survival (OS) (HR=2.19, 95%CI: 1.70-2.82) and progression-free survival (PFS) (HR=2.59, 95% CI: 1.78-3.76). Moderate heterogeneity was observed in meta-analysis for LNM. However, the results remained robust in multiple sensitivity analyses. Conclusions: High expression of CCAT2 was linked with poor clinical outcome. CCAT2 can serve as a potential molecular marker for prognosis in different types of cancers., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.