Long Non-coding RNA EBLN3P Regulates UHMK1 Expression by Sponging miR-323a-3p and Promotes Colorectal Cancer Progression

Xu, Xiang-hao; Song, Wen; Li, Junhua; Huang, Zeqi; Liu, Ya‐fang; Bao, Qiang; Shen, Zhiwen

doi:10.3389/fmed.2021.651600

Cited by 24 publications

(26 citation statements)

References 29 publications

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“…Therefore, the signaling pathways underlying the observed UHMK1-regulated progression of PDAC are quite complex and involve the regulation of UHMK1 by lncRNA H19 according to our findings. However, H19 is not the only lncRNA involved in UHMK1 regulation because Xu et al., 2021 stated that lncRNA EBLN3P regulates UHMK1 expression by sponging miR323a-3p, thereby promoting colorectal cancer progression ( 29 ). Although it is unknown whether the latter described mechanism is also involved in PDAC progression, our data were consistent with the notion that reduced expression of H19 inhibits PDAC metastasis, which involves the H19-mediated regulation of miR-194 and let-7 ( 6 , 10 , 30 ).…”

Section: Discussionmentioning

confidence: 99%

UHMK1 Is a Novel Marker for Personalized Prediction of Pancreatic Cancer Prognosis

et al. 2022

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Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of cancer mortality, and new therapeutic options are urgently needed. Long noncoding RNA H19 (H19) is known to promote PDAC progression, but the downstream genes of H19 are largely unknown. Five PDAC cell lines, nonmalignant pancreatic cells, TCGA, GEO-derived pancreatic tissues (malignant, n=413; nonmalignant, n=234), a pancreatic tissue array (n=96), and pancreatic tissues from our clinic (malignant, n=20; nonmalignant, n=20) were examined by a gene array, RT-qPCR, Western blotting, MTT, colony formation, wound-healing, siRNA-mediated gene silencing, bioinformatics, xenotransplantation, and immunohistochemistry assays. The cell cycle inhibitor, UHMK1, was identified to have the strongest correlation with H19. UHMK1 expression was enhanced in PDAC, and high UHMK1 expression correlated with tumor stage, and lower overall survival. siRNA-mediated UHMK1 downregulation inhibited progression signaling. siRNA-mediated downregulation of H19 or UHMK1 inhibited tumor proliferation and xenograft growth. Based on the correlation between UHMK1 expression and clinical parameters, we developed a nomogram that reliably predicts patient prognosis and overall survival. Together, we characterized UHMK1 as an H19-induced oncogene and verified it as a novel PDAC prognostic marker for overall survival.

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Section: Discussionmentioning

confidence: 99%

UHMK1 Is a Novel Marker for Personalized Prediction of Pancreatic Cancer Prognosis

et al. 2022

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“…UHMK1 also contributes to purine metabolism reprogramming by regulating the NCOA3/ATF4 axis and significantly promotes gastric cancer development [ 21 ]. A recent study showed that EBLN3P promotes tumor development via targeting miR-323a-3p/UHMK1 in CRC [ 33 ]. In addition, UHMK1 expression is under the control of oxidative phosphorylation [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

UHMK1 aids colorectal cancer cell proliferation and chemoresistance through augmenting IL-6/STAT3 signaling

et al. 2022

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UHMK1, a serine/threonine kinase with a U2AF homology motif, is implicated in RNA processing and protein phosphorylation. Increasing evidence has indicated its involvement in tumorigenesis. However, it remains to be elucidated whether UHMK1 plays a role in the development of colorectal cancer (CRC). Here, we demonstrated that UHMK1 was frequently upregulated in CRC samples compared with adjacent normal tissue and high expression of UHMK1 predicted poor outcomes. Knockdown of UHMK1 by siRNAs restrained CRC cell proliferation and increased oxaliplatin sensitivity, whereas overexpression of UHMK1 promoted CRC cell growth and oxaliplatin resistance, suggesting that UHMK1 plays important oncogenic roles in CRC. Mechanistically, we showed that UHMK1 had a significant effect on IL6/STAT3 signaling by interacting with STAT3. The interaction of UHMK1 with STAT3 enhanced STAT3 activity in regulating gene transcription. Furthermore, we found that STAT3 could in turn transcriptionally activate UHMK1 expression in CRC cells. The complementary experiments for cell growth and oxaliplatin resistance indicated the interdependent relationship between UHMK1 and STAT3. Thus, these collective findings uncovered a new UHMK1/STAT3 positive feedback regulatory loop contributing to CRC development and chemoresistance.

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“…miR-323a-3p is located on chromosome 14q32.31 and acts as a tumor suppressor gene in CRC [ 36 ]. Furthermore, it has been found that the upregulation of miR-323a-3p expression can induce apoptosis and inhibit the proliferation and migration of glioma cells by targeting IGF-1R [ 37 ] and damage the progression of epithelial-mesenchymal transition in bladder cancer cells by regulating the MET/SMAD3/SNAIL circuit [ 38 ] and negatively regulate LDHA expression to disrupt glycolysis in osteosarcoma cells [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-323a-3p Negatively Regulates NEK6 in Colon Adenocarcinoma Cells

Hong

Chen

Pan

et al. 2022

Journal of Oncology

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Objective. The activity of NEK6 is enhanced in several cancer cells, including colon adenocarcinoma (COAD) cells. However, there are few reports on the microRNA (miRNA/miR) regulation of NEK6. In this study, we aimed to investigate the effects of miRNAs targeting NEK6 in COAD cells. Methods. Public data and online analysis sites were used to analyze the expression levels of NEK6 and miR-323a-3p in COAD tissues as well as the relationship between NEK6 or miR-323a-3p levels and survival in patients with COAD and to predict miRNAs targeting NEK6. Real-time polymerase chain reaction and western blotting were performed to determine the levels of NEK6 and miR-323a-3p in COAD cells. The targeting of NEK6 by miR-323a-3p was verified using a dual-luciferase reporter assay. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 5-ethynyl-2′-deoxyuridine assay, propidium iodide (PI) staining, annexin V-fluorescein isothiocyanate/PI staining, and transwell assay were employed to test the proliferation, apoptosis, migration ability, and invasiveness of COAD cells. Results. In COAD cells, NEK6 was highly expressed, whereas miR-323a-3p was expressed at low levels and negatively regulated NEK6. Upregulating the level of miR-323a-3p impaired the proliferation, migration, and invasion of COAD cells and promoted apoptosis, whereas supplementing NEK6 alleviated the damage of the proliferation, migration, and invasion of COAD cells caused by miR-323a-3p and inhibited miR-323a-3p-induced apoptosis. These findings indicate that miR-323a-3p regulates the proliferation, migration, invasion, and apoptosis of COAD cells by targeting NEK6. Conclusion. miR-323a-3p downregulates NEK6 in COAD cells; this provides a novel basis for further understanding the occurrence and development of COAD.

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Long Non-coding RNA EBLN3P Regulates UHMK1 Expression by Sponging miR-323a-3p and Promotes Colorectal Cancer Progression

Cited by 24 publications

References 29 publications

UHMK1 Is a Novel Marker for Personalized Prediction of Pancreatic Cancer Prognosis

UHMK1 Is a Novel Marker for Personalized Prediction of Pancreatic Cancer Prognosis

UHMK1 aids colorectal cancer cell proliferation and chemoresistance through augmenting IL-6/STAT3 signaling

MicroRNA-323a-3p Negatively Regulates NEK6 in Colon Adenocarcinoma Cells

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