Long non-coding RNA LUCAT1 promotes proliferation and invasion in gastric cancer by regulating miR-134-5p/YWHAZ axis

Chi, Jun-Lin; Liu, Tonglei; Shi, Chengmin; Luo, Huayou; Wu, Zhi‐Zhong; Xiong, Bin; Liu, Shuang; Zeng, Yujian

doi:10.1016/j.biopha.2019.109201

Cited by 46 publications

(38 citation statements)

References 23 publications

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“…Since LUCAT1 was first introduced in 2013 under the name of smoke and cancer-associated lncRNA-1 (SCAL1), it has been shown to be expressed in serous ovarian cancer, clear cell renal cell carcinoma, colorectal cancer, bladder cancer, osteosarcoma, glioma, esophageal, head and neck squamous cell carcinoma, prostate, hepatocellular carcinoma, triple negative breast cancer, and cervical cancer. Chi, et al 37 reported that LUCAT1 promotes GC by regulating the miR-134-5p/YWHAZ axis. Here, we found that LUCAT1 expression was higher in GC tissue than in adjacent non-tumor tissue.…”

Section: Discussionmentioning

confidence: 99%

“…Alteration of the methylation status of CXXC4 or mutation of this gene have been reported in GC. 37 We examined the methylation status of CXXC4 and SFRP2 in non-tumor and cancer tissues from five patients, and found that these two genes were more highly methylated in cancer tissue than in non-tumor tissue. We also found that siLUCAT1 reduced methylation of CXXC4 and SFRP2 in GC cells.…”

Section: Discussionmentioning

confidence: 99%

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LUCAT1 Epigenetically Downregulates the Tumor Suppressor Genes CXXC4 and SFRP2 in Gastric Cancer

2020

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Purpose The mechanisms of Wnt/β-catenin pathway signaling and abnormal expression of tumor suppressor genes is not well known in gastric cancer (GC). Long non-coding RNA (lncRNA) has recently been identified as a possible link therein. In this study, we investigated the role of lung cancer associated transcript 1 (LUCAT1) in GC. Materials and Methods The expression of LUCAT1 in GC cell lines and 100 tissue samples was examined by qRT-PCR. Two different siRNAs were used for knockdown of LUCAT1 expression. Cell viability was assessed by MTT assay. To analyze metastasis, scratch wound-healing assay, a Matrigel invasion assay, and colony formation assay were performed. Apoptosis was analyzed by PI/Annexin-V staining. To check the methylation status in tumor suppressor genes, methylation-specific PCR was carried out. Western blot was performed to detect epithelial-mesenchymal transition and apoptosis markers upon silencing of LUCAT1 (siLUCAT1). Results LUCAT1 expression in GC cell lines and tissues was significantly elevated, compared to that in normal gastric cells and adjacent non-tumor tissues ( p <0.001). Two different siRNAs for LUCAT1 reduced cell proliferation, invasion, and migration, compared to siCT ( p <0.05), and these reductions were restored by pcDNA-LUCAT1 ( p <0.05). siLUCAT1 elicited upregulation of the expression of CXXC4 and SFRP2 . The expression of H3K27me3 was reduced by siLUCAT1, and this reduction was correlated with methylation of CXXC4 and SFRP2 . Inhibition of LUCAT1 up-regulated EZH2 expression and resulted in demethylation of CXXC4 and SFRP2 through the Wnt/β-catenin signaling pathway. Conclusion We concluded that LUCAT1 induces methylation of CXXC4 and SFRP2 , thereby regulating Wnt/β-catenin signaling in GC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

LUCAT1 Epigenetically Downregulates the Tumor Suppressor Genes CXXC4 and SFRP2 in Gastric Cancer

2020

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“…In gastric cancer, long non-coding RNA LUCAT1 was negatively correlated with miR-134-5p and miR-134-5p was negatively related with YWHAZ [61]. Knockdown of LUCAT1 inhibited YWHAZ expression, which can be reversed by miR-134-5p inhibitor [61]. Similarly, long non-coding RNA SNHG14, acting as a miR-206 sponge and decreasing its expression, increased YWHAZ expression in cervical cancer [62] and long non-coding RNA LINC00858 regulated YWHAZ by inhibiting miR-22-3p in colorectal cancer [63].…”

Section: Upstream Regulators Of Ywhazmentioning

confidence: 98%

“…Recently, long non-coding RNAs, more than 200nt and involved in multiple cell processes, are emerging as competing endogenous RNAs to regulate YWHAZ by targeting miRNAs [61][62][63]. In gastric cancer, long non-coding RNA LUCAT1 was negatively correlated with miR-134-5p and miR-134-5p was negatively related with YWHAZ [61]. Knockdown of LUCAT1 inhibited YWHAZ expression, which can be reversed by miR-134-5p inhibitor [61].…”

Section: Upstream Regulators Of Ywhazmentioning

confidence: 99%

The role of YWHAZ in cancer: A maze of opportunities and challenges

Gan

Feng

2020

J. Cancer

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YWHAZ (also named 14-3-3ζ) is a central hub protein for many signal transduction pathways and plays a significant role in tumor progression. Accumulating evidences have demonstrated that YWHAZ is frequently up-regulated in multiple types of cancers and acts as an oncogene in a wide range of cell activities including cell growth, cell cycle, apoptosis, migration, and invasion. Moreover, YWHAZ was reported to be regulated by microRNAs (miRNAs) or long non-coding RNAs and exerted its malignant functions by targeting downstream molecules like protein kinase, apoptosis proteins, and metastasis-related molecules. Additionally, YWHAZ may be a potential biomarker of diagnosis, prognosis and chemoresistance in several cancers. Targeting YWHAZ by siRNA, shRNA or miRNA was reported to have great help in suppressing malignant properties of cancer cells. In this review, we perform literature and bioinformatics analysis to reveal the oncogenic role and molecular mechanism of YWHAZ in cancer, and discuss the potential clinical applications of YWHAZ concerning diagnosis, prognosis, and therapy in malignant tumors.

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“…YWHAZ has been shown to be overexpressed in multiple types of cancers and regulated by miRNAs or lncRNAs (14). Zeng Y et al reported that lncRNA LUCAT1/miR-134-5p/YWHAZ axis can promote proliferation and invasion of GC (15); Wang H et al found circ-SERPINE2/miR-375/YWHAZ axis promote proliferation (16) and Jin CX et al clari ed how YWHAZ effects apoptosis and autophagy in GC (17). In this study, we demonstrate that SNHG12 shows promise as a possible biomarker and therapeutic target in GC and how SNHG12 regulates the β-catenin signaling pathway by modulating the YWHAZ protein.…”

Section: Introductionmentioning

confidence: 99%

YY1-modulated Long Non-coding RNA SNHG12 Predicts and Promotes Gastric Cancer Metastasis via Activating miR-218-5p/YWHAZ-dependent β-catenin: A Bed to Bench Approach

Zhang¹,

Dai²,

Beeharry³

et al. 2020

Preprint

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Background: Gastric Cancer (GC) is one of the leading causes of cancer-related deaths and mortality. Long non-coding RNAs (lncRNAs) such as SNHG12 play important roles in the pathogenesis and progression of cancers. However, the role and significanve of SNHG12 in the metastasis of GC has not yet been thoroughly investigated.Methods: The SNHG12 expression pattern was detected in GC tissue samples from our faculty and cell lines using quantitative reverse transcription PCR. In vivo and in vitro gain and loss assays were conducted to observe the effects of SNHG12 regulation on GC cell metastasis potential. The underlying mechanisms of SNHG12 regulation on EMT and metastatic potential of GC cells were further determined by quantitative reverse transcription PCR, western blotting, dual luciferase reporter assays, co-immunoprecipitation, immunoprecipitation, RIP assays, TOPFlash/FOPFlash reporter assays and Ch-IP assays.Results: SNHG12 was upregulated in GC tissues and cell lines. The expression levels of SNHG12 in GC samples was significantly related to tumor invasion depth, TNM staging and lymph node metastasis, and was associated with poorer DFS and OS in the GC patients. SNHG12 was significantly highly expressed in peritoneal metastatic tissues from GC patients and mice subjects, suggesting a possible role of SNHG12 in peritoneal carcinomatosis from GC. Further in vivo and in vitro gain and loss assays indicated that SNHG12 promoted GC metastasis and EMT. Based on hypothetical bioinformatic analysis findings, our mechanistic analyses revealed that miR-218-5p was a direct target of SNHG12 and suggested that both SNHG12 and miR-218-5p could collectively regulate YWHAZ, forming the SNHG12/ miR-218-5p/YWHAZ axis, hereby decreasing the ubiquitination of β-catenin, thus activating the β-catenin signaling pathway and facilitating metastasis and EMT. Further analysis also revealed that the transcription factor YY1 could negatively modulate SNHG12 transcription.Conclusions: Our findings demonstrate that SNHG12 is be a potential prognostic marker and therapeutic target for GC. Negatively modulated by transcription factor YYI, SNHG12 promotes GC metastasis and EMT by regulating the miR-218-5p/YWHAZ axis and hence activating the β-catenin signaling pathway. Furthermore, we discovered high SNHG12 expression could be related to peritoneal carcinomatosis from GC but this requires further validation.

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Long non-coding RNA LUCAT1 promotes proliferation and invasion in gastric cancer by regulating miR-134-5p/YWHAZ axis

Cited by 46 publications

References 23 publications

LUCAT1 Epigenetically Downregulates the Tumor Suppressor Genes CXXC4 and SFRP2 in Gastric Cancer

LUCAT1 Epigenetically Downregulates the Tumor Suppressor Genes CXXC4 and SFRP2 in Gastric Cancer

The role of YWHAZ in cancer: A maze of opportunities and challenges

YY1-modulated Long Non-coding RNA SNHG12 Predicts and Promotes Gastric Cancer Metastasis via Activating miR-218-5p/YWHAZ-dependent β-catenin: A Bed to Bench Approach

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