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Pepsinogen C expression–related lncRNA/circRNA/mRNA profile and its co-mediated ceRNA network in gastric cancer

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Abstract

The expression of pepsinogen C (PGC) is considered an ideal negative biomarker of gastric cancer, but its pathological mechanisms remain unclear. This study aims to analyze competing endogenous RNA (ceRNA) networks related to PGC expression at a post-transcriptional level and build an experimental basis for studying the role of PGC in the progression of gastric cancer. RNA sequencing technology was used to detect the differential expression (DE) profiles of PGC-related long non-coding (lnc)RNAs, circular (circ)RNAs, and mRNAs. Ggcorrplot R package and online database were used to construct DElncRNAs/DEcircRNAs co-mediated PGC expression–related ceRNA networks. In vivo and in vitro validations were performed using quantitative reverse transcription–PCR (qRT-PCR). RNA sequencing found 637 DEmRNAs, 698 DElncRNAs, and 38 DEcircRNAs. The PPI network of PGC expression–related mRNAs consisted of 503 nodes and 1179 edges. CFH, PPARG, and MUC6 directly interacted with PGC. Enrichment analysis suggested that DEmRNAs were mainly enriched in cancer-related pathways. Eleven DElncRNAs, 13 circRNAs, and 35 miRNA–mRNA pairs were used to construct ceRNA networks co-mediated by DElncRNAs and DEcircRNAs that were PGC expression–related. The network directly related to PGC was as follows: SNHG16/hsa_circ_0008197–hsa-mir-98-5p/hsa-let-7f-5p/hsa-let-7c-5p–PGC. qRT-PCR validation results showed that PGC, PPARG, SNHG16, and hsa_circ_0008197 were differentially expressed in gastric cancer cells and tissues: PGC positively correlated with PPARG (r = 0.276, P = 0.009), SNHG16 (r = 0.35, P = 0.002), and hsa_circ_0008197 (r = 0.346, P = 0.005). PGC-related DElncRNAs and DEcircRNAs co-mediated complicated ceRNA networks to regulate PGC expression, thus affecting the occurrence and development of gastric cancer at a post-transcriptional level. Of these, the network directly associated with PGC expression was a SNHG16/hsa_circ_0008197–mir-98-5p/hsa-let-7f-5p/hsa-let-7c-5p – PGC axis. This study may form a foundation for the subsequent exploration of the possible regulatory mechanisms of PGC in gastric cancer.

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Data availability

The data that support the results of this manuscript are available from the corresponding author upon reasonable request.

Code availability

Not applicable.

Abbreviations

PGC:

Pepsinogen C

ceRNA:

Competing endogenous RNA

DE:

Differentially expressed

lncRNAs:

Long non-coding RNAs

circRNAs:

Circular RNAs

PPI:

Protein–protein interaction

miRNA:

MicroRNA

GO:

Gene Ontology

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Funding

The authors received financial support from the National Natural Science Foundation of China (No.81772987).

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Author notes

  1. Li-rong Yan and Han-xi Ding contributed equally to this work

Authors and Affiliations

  1. Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning Provincial Education Department, 110001, Shenyang, China

    Li-rong Yan, Han-xi Ding, Shi-xuan Shen, Xiao-dong Lu, Yuan Yuan & Qian Xu

Authors
  1. Li-rong Yan
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  2. Han-xi Ding
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  3. Shi-xuan Shen
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  4. Xiao-dong Lu
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  5. Yuan Yuan
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  6. Qian Xu
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Contributions

Yuan Yuan and Qian Xu conceived and designed this study. Li-rong Yan, Han-xi Ding, Shi-xuan Shen, and Xiao-dong Lu were responsible for the data analysis and performed data interpretation. Li-rong Yan and Han-xi Ding wrote the paper. Qian Xu and Yuan Yuan revised the manuscript.

Corresponding authors

Correspondence to Yuan Yuan or Qian Xu.

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Ethics approval

The study was supported by the research ethics committee of the First Affiliated Hospital of China Medical University ([2021]94).

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The written informed consents in this study were signed by all patients.

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All co-authors have agreed to publish the paper.

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The authors declare no competing interests.

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Yan, Lr., Ding, Hx., Shen, Sx. et al. Pepsinogen C expression–related lncRNA/circRNA/mRNA profile and its co-mediated ceRNA network in gastric cancer. Funct Integr Genomics 21, 605–618 (2021). https://doi.org/10.1007/s10142-021-00803-x

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