Comprehensive analysis of lncRNA-miRNA-mRNA regulatory networks for microbiota-mediated colorectal cancer associated with immune cell infiltration

Xiangzhou Tan; Linfeng Mao; Changhao Huang; Weimin Yang; Jianping Guo; Zhikang Chen; Zihua Chen

doi:10.1080/21655979.2021.1940614

Comprehensive analysis of lncRNA-miRNA-mRNA regulatory networks for microbiota-mediated colorectal cancer associated with immune cell infiltration

Bioengineered. 2021 Dec;12(1):3410-3425. doi: 10.1080/21655979.2021.1940614.

Authors

Xiangzhou Tan^{1

2

3}, Linfeng Mao^{1

3}, Changhao Huang^{1

3}, Weimin Yang^{1

3}, Jianping Guo^{1

3}, Zhikang Chen^{1

3}, Zihua Chen^{1

3}

Affiliations

¹ Hunan Key Laboratory of Precise Diagnosis and Treatment of Gastrointestinal Tumor, Xiangya Hospital Central South University, Changsha, Hunan Province, China.
² Department of General, Visceral and Transplant Surgery, University Hospital Tuebingen, Tuebingen, Baden-Wuerttemberg, Germany.
³ Department of General Surgery, Xiangya Hospital Central South University, Changsha, Hunan Province, China.

Abstract

Recent findings have identified microbiota as crucial participants in many disease conditions, including cancers. Competing endogenous RNA (ceRNA) is regarded as a candidate mechanism involving relevant biological processes. We therefore constructed a ceRNA network using the TCGA and GEO database, to determine the potential mechanisms of microbiota-mediated colorectal carcinogenesis and progression. We found a total of 75 lncRNAs, 8 miRNAs, and 9 mRNAs in the probiotics-mediated ceRNA network and a total of 49 lncRNAs, 4 miRNAs, and 3 mRNA in the pathobiont-mediated ceRNA network, which could induce the microbiota-mediated carcinogenesis and progression. The GO and KEGG analysis indicated that the ceRNA network is mainly enriched in the metabolic process, and two unique pathways (the p53 signaling pathway and microRNA in cancer), respectively. A four-gene signature (FRMD6-AS2, DIRC3, LIFR-AS1, and MRPL23-AS1) was suggested as an independent prognostic factor. Four lncRNAs (LINC00355, KCNQ1OT1, LINC00491, and HOTAIR) were associated with poor survival. Three small molecule candidate anticancer drugs (Pentoxyverine, Rimexolone, and Doxylamine) were identified. A four-gene signature (FAM129A, BCL2, PMAIP1, and RPS6) is significantly correlated with immune infiltration level. This study provides a promising biomarker reservoir to explore the mechanism by which microbiota regulate the ceRNA network involving the immune response, and further participate in colorectal carcinogenesis and progression.

Keywords: Cerna network; bioinformatics; colorectal cancer; immune infiltration; lncRNA; miRNA; microbiota.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / pharmacology
Colorectal Neoplasms* / diagnosis
Colorectal Neoplasms* / genetics
Colorectal Neoplasms* / mortality
Colorectal Neoplasms* / pathology
Computational Biology
Gastrointestinal Microbiome / genetics*
Gene Expression Regulation, Neoplastic / genetics
Gene Regulatory Networks / drug effects
Gene Regulatory Networks / genetics*
Humans
Prognosis
Protein Interaction Maps / drug effects
RNA, Messenger / genetics*
RNA, Messenger / metabolism
RNA, Untranslated / genetics*
RNA, Untranslated / metabolism

Substances

Antineoplastic Agents
RNA, Messenger
RNA, Untranslated

Grants and funding

This study was funded by the National Natural Science Foundation of China, grant number 81472692 and 81573012. And it was also supported by the program of China Scholarships Council, grant number 201806370236;the program of China Scholarships Council [201806370236];