Dataset Information

Long non-coding RNA Lnc-LALC facilitates colorectal cancer liver metastasis via epigenetically silencing LZTS1.

ABSTRACT: Colorectal cancer (CRC) is one of the most common cancers around the world and endangers human health seriously. Liver metastasis is an important factor affecting the long-term prognosis of CRC and the specific mechanism of CRLM (colorectal cancer with liver metastasis) is not fully understood. LZTS1 has been found dysregulated in many cancers, especially in CRC. Theories suggested that hypermethylation of the promoter regions of LZTS1 was responsible for LZTS1 abnormal expression in multiple malignant tumors. Although the role of LZTS1 in CRC cell proliferation has been reported, its role in CRLM remains unclear. Numerous studies reported Long non-coding RNA (lncRNA) could regulate the gene expression level by regulating gene methylation status in many tumors. However, whether there were lncRNAs could change the methylation status of LZTS1 or not in CRLM was unknown. In this study, we aimed to investigate whether there are lncRNAs can regulate the expression of LZTS1 through affecting DNA methylation in CRLM. We found that upregulated Lnc-LALC in CRC was negatively correlated with LZTS1 expression, and Lnc-LALC could regulate LZTS1 expression in both mRNA and protein level in our study. Functionally, Lnc-LALC enhanced the CRC cells metastasis ability in vitro and vivo through inhibiting the expression of LZTS1. Furthermore, the precise mechanisms exploration showed that lnc-LALC could recruit DNA methyltransferases (DNMTs) to the LZTS1 promoter by combining with Enhancer of zeste homolog 2(EZH2) and then altered the expression of LZTS1 via DNMTs-mediated DNA methylation. Collectively, our data demonstrated the important role of Lnc-LALC/ LZTS1 axis in CRLM development.

SUBMITTER: Zhang C

PROVIDER: S-EPMC7910484 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Long non-coding RNA Lnc-LALC facilitates colorectal cancer liver metastasis via epigenetically silencing LZTS1.

Zhang Chuan C Wang Lu L Jin Chi C Zhou Jiahui J Peng Chaofan C Wang Yong Y Xu Ziwei Z Zhang Dongsheng D Huang Yuanjian Y Zhang Yue Y Ji Dongjian D Peng Wen W Jin Kangpeng K Tang Junwei J Feng Yifei Y Sun Yueming Y

Cell death & disease 20210226 2

Colorectal cancer (CRC) is one of the most common cancers around the world and endangers human health seriously. Liver metastasis is an important factor affecting the long-term prognosis of CRC and the specific mechanism of CRLM (colorectal cancer with liver metastasis) is not fully understood. LZTS1 has been found dysregulated in many cancers, especially in CRC. Theories suggested that hypermethylation of the promoter regions of LZTS1 was responsible for LZTS1 abnormal expression in multiple ma ...[more]

PMID: 33637680

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Project description:Long non-coding RNAs (lncRNAs) participate in various biological processed involved in tumorigenesis, metastasis and proliferation. The aim of the present study was to identify candidate long non-coding RNAs (lncRNAs) involved in sentinel lymph node (SLN) metastasis in breast cancer. Specimens of SLNs were collected from patients with SLN metastasis via punch biopsy. Total RNA was extracted and RNA sequencing (RNA-seq) was conducted. Differential expression profiles of mRNAs and lncRNAs were obtained via bioinformatics analysis, and Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on differentially expressed mRNAs. The expression levels of lncRNAs were analyzed via reverse transcription-quantitative PCR (RT-qPCR), and the regulation network of the lncRNAs to downstream microRNAs (miRs) and mRNAs was predicted. Based on RNA-seq results, six differentially expressed candidate lncRNAs were identified in patients with and without SLN metastasis: lnc-ANGPTL1-3:3, lnc-GJA10-12:1, lnc-ACAN-2:1, lnc-ZPBP2-4:1, lnc-GATA3-16:1 and lnc-ACOX3-5:1. KEGG and GO analysis identified that the mitogen-activated protein kinase (MAPK) and PI3K/Akt signaling pathways were the most enriched pathways. After RT-qPCR analysis, lnc-ANGPTL1-3:3 and lnc-GJA10-12:1 exhibited expression patterns that were consistent with those from RNA-seq. Moreover, receiver operating characteristic curve analysis demonstrated that lnc-ANGPTL1-3:3 and lnc-GJA10-12:1 expression levels had high sensitivity and specificity in the diagnosis of SLN metastasis, and that their expression levels were upregulated in patients with axillary lymph node metastasis. Further analysis revealed that lnc-GJA10-12:1 and lnc-ANGPTL1-3:3 were commonly involved in regulating the miR-302 family, including miR-302d-3p and miR-302c-3p, which together targeted AKT1. Additionally, lnc-ANGPTL1-3:3 was predicted to target miR-520b to regulate MAP3K2 expression. lnc-GJA10-12:1 was also predicted to target miR-34a-5p to regulate MAP2K1 and MAP3K9 expression levels, as well as miR-449a to regulate MAP2K1 expression. The results of the present study suggested that lnc-ANGPTL1-3:3 and lnc-GJA10-12:1 may potentially serve a role in SLN metastasis of breast cancer by regulating the PI3K/Akt and MAPK signaling pathways via targeting the miR-302 family, miR-520a-3p, miR-34a-5p and miR-449a. Thus, lnc-ANGPTL1-3:3 and lnc-GJA10-12:1 in SLN may serve as potential markers of breast cancer metastasis.

Dataset Information

Long non-coding RNA Lnc-LALC facilitates colorectal cancer liver metastasis via epigenetically silencing LZTS1.

Publications

Long non-coding RNA Lnc-LALC facilitates colorectal cancer liver metastasis via epigenetically silencing LZTS1.

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