Overexpression of HOXA10 is associated with unfavorable prognosis of acute myeloid leukemia

Abstract

Background HOXA family genes were crucial transcription factors involving cell proliferation and apoptosis. While few studies have focused on HOXA10 in AML. We aimed to investigate the prognostic significance of HOXA10. Methods We downloaded datasets from GEO and BeatAML database, to compare HOXA expression level between AML patients and controls. Kaplan-Meier curves were used to estimate the impact of HOXA10 expression on AML survival. The differentially expressed genes, miRNAs, lncRNAs and methylated regions between HOXA10-high and -low groups were obtained using R (version 3.6.0). Accordingly, the gene set enrichment analysis (GSEA) was accomplished using MSigDB database. Moreover, the regulatory TFs/microRNAs/lncRNAs of HOXA10 were identified. A LASSO-Cox model fitted OS to clinical and HOXA10-associated genetic variables by glmnet package. Results HOXA10 was overexpressed in AML patients than that in controls. The HOXA10-high group is significantly associated with shorter OS and DFS. A total of 1219 DEGs, 131 DEmiRs, 282 DElncRs were identified to be associated with HOXA10. GSEA revealed that 12 suppressed and 3 activated pathways in HOXA10-high group. Furthermore, the integrated regulatory network targeting HOXA10 was established. The LASSO-Cox model fitted OS to AML-survival risk scores, which included age, race, molecular risk, expression of IKZF2/LINC00649/LINC00839/FENDRR and has-miR-424-5p. The time dependent ROC indicated a satisfying AUC (1-year AUC 0.839, 3-year AUC 0.871 and 5-year AUC 0.813). Conclusions Our study identified HOXA10 overexpression as an adverse prognostic factor for AML. The LASSO-COX regression analysis revealed novel prediction model of OS with superior diagnostic utility.

Long non-coding RNA LINC00649 regulates YES-associated protein 1 (YAP1)/Hippo pathway to accelerate gastric cancer (GC) progression via sequestering miR-16-5p

“…As previously described, miR-16-5p played a tumor-suppressing effects to slow down cancer progression [19][20][21], including GC [22][23][24], which evidenced the opposite effects of LINC00649 and miR-16-5p in regulating GC development. Thus, we performed further gain-and loss-of-function experiments, and expectedly found that knockdown of LINC00649 suppressed GC pathogenesis via releasing miR-16-5p, which were partially supported by the previous publications [10][11][12][13][22][23][24].…”

“…Although emerging data suggested that targeting LncRNAs was effective to hamper cancer progression and improve drug-resistance in GC, and multiple LncRNAs had been identified as diagnostic, therapeutic and prognostic biomarkers for GC, the involvement of a novel LncRNA LINC00649 in regulating GC pathogenesis had not been studied. Based on the information provided by the previous literatures, LINC00649 acted as an oncogene to facilitate the development of acute myeloid leukemia (AML) [10,11], prostate cancer [12] and colorectal cancer [13], but it was still unclear whether LINC00649 modulated GC progression in a similar manner. Hence, by conducting clinical and preliminary experiments, this study assured that LINC00649 also exerted its tumor-promoting effects in GC, which were in consistent with the previous publications in other types of cancers [10][11][12][13].…”

“…Based on the information provided by the previous literatures, LINC00649 acted as an oncogene to facilitate the development of acute myeloid leukemia (AML) [10,11], prostate cancer [12] and colorectal cancer [13], but it was still unclear whether LINC00649 modulated GC progression in a similar manner. Hence, by conducting clinical and preliminary experiments, this study assured that LINC00649 also exerted its tumor-promoting effects in GC, which were in consistent with the previous publications in other types of cancers [10][11][12][13]. Specifically, our data evidenced that LINC00649 tended to be enriched in GC tissues and cells, in contrast with the normal counterparts, and LINC00649 positively regulated GC cell proliferation, migration, epithelialmesenchymal transition (EMT) and tumorigenesis in vitro and in vivo, hinting that LINC00649 served as an oncogene for GC.…”

“…To our knowledge, LINC00649 is identified as an important prognostic marker for acute myeloid leukemia (AML) [10,11], prostate cancer [12] and colorectal cancer [13], but its role in other types of cancers had not been reported.…”

LINC00649 underexpression is an adverse prognostic marker in acute myeloid leukemia

“…LINC00649, which we focused in the research, was identified as a prognostic marker in prostate and colorectal cancers by previous bioinformatic analysis [12,13]. Few studies have investigated the prognostic value of LINC00649 in AML [14]. Notably, the expression of LINC00649 was significantly correlated with HOXA family genes, indicated by the results derived from GEPIA [15] 2.0 online tools (http://gepia2.cancer-pku.cn/) and our own analysis.…”