MiR-148a-3p targets CEMIP to suppress the genesis of gastric cancer cells

https://doi.org/10.1016/j.bbrc.2021.08.039Get rights and content

Highlights

  • Upregulation of CEMIP in gastric cancer.

  • CEMIP facilitated proliferation and adhesion, but repressed cell apoptosis of gastric cancer cells.

  • MiR-148a-3p inhibited the expression of CEMIP in gastric cancer.

  • MiR-148a-3p hampered gastric cancer cell progression by inhibiting CEMIP.

  • The identification of CEMIP and miR-375 in gastric cancer.

Abstract

Background

Gastric cancer is the sixth common malignancy worldwide. Dysregulation of Cell Migration Inducing Hyaluronidase 1 (CEMIP) gene and microRNA-148a -3p (miR-148a-3p) expressions has been found in gastric cancer genesis. However, the underlying molecular mechanism in gastric cancer needs further investigation.

Methods

The expression of gastric cancer tissues' and cells’ CEMIP and miR-148a-3p were examined by RT-qPCR. The interaction between miR-148a-3p and CEMIP was verified by luciferase activity detection. Cell viability, proliferation, adhesion, and apoptosis in gastric cancer GTL-16 and AGS cells were analyzed by CCK8, BrdU, cell adhesion, and FITC assay.

Results

CEMIP expression was significantly elevated, but the miR-148a-3p level was downregulated in gastric cancer tissues and cell lines. Overexpression of CEMIP accelerated cell viability, proliferation, and adhesion, but attenuated cell apoptosis of gastric cancer cells. In addition, upregulation of miR-148a-3p repressed the development of gastric cancer in vitro. Moreover, miR-148a-3p suppressed gastric cancer tumorigenesis by inhibiting the expression of CEMIP.

Conclusion

The study clarified that miR-148a-3p suppressed gastric cancer tumorigenesis by inhibiting CEMIP, which may be effective targets for the clinical treatment of gastric cancer.

Introduction

Gastric cancer is the sixth common and aggressive malignancy and the second leading cause of cancer-related death worldwide [1]. Recent years, the mortality of gastric cancer was significant decreased since the promoted surgical resection in early stage of gastric cancer patients, but advanced stage of gastric cancer showed unsatisfying efficacy [2,3]. Therefore, exploring the underlying molecular mechanism in the pathological of gastric cancer is important for clinical treatment of patients with gastric cancer.

Cell Migration Inducing Hyaluronidase 1 (CEMIP) gene, consisting of 30 exons, locates on chromosome 15q25.1. It promotes epithelial-mesenchymal transition (EMT), and tumor cell growth, invasion and cancer dissemination [4,5]. Increasing evidences suggested that CEMIP was associated with tumorigenesis and progression, such breast cancer, prostate cancer, and ovarian cancer [[6], [7], [8]]. For instance, CEMIP activated STAT3 pathway to facilitate cell proliferation and migration in breast cancer [6]. Additionally, CEMIP regulating PI3K/AKT signaling pathway and facilitated ovarian cancer genesis [9]. Unfortunately, the biological role of CEMIP in gastric cancer remains unknown yet.

MicroRNAs (miRNAs) are small non-coding RNAs with approximately 22 nucleotides serving as gene regulators through modulating the expression of the downstream genes [10]. Accumulating evidences have clarified the key role of the abnormal miRNAs in regulating cancer genesis [11,12]. MiR-148a-3p was identified as an important modulator in different type of cancers by regulating cell growth and apoptosis, such as pancreatic cancer, breast cancer, and lung cancer [[13], [14], [15]]. For example, miRNA-148a-3p suppressed EMT and stemness properties through regulating Wnt/β-catenin pathway of pancreatic cancer cells [13]. Several studies also reported that miRNA-148a-3p exerted inhibition roles in gastric cancer [[16], [17], [18]]. Nevertheless, whether miR-148a-3p-CEMIP axis took part in the progression of gastric cancer need further investigation.

Our study sought to provide a comprehensive of the biological role of miR-148a-3p-CEMIP axis on gastric cancer. It is hypothesized that miR-148a-3p inhibits CEMIP to repress the progression of gastric cancer, which might provide a new direction for gastric cancer therapy.

Section snippets

Tissue specimens, cell lines, and cell transfection

We collected cancer tissues and corresponding normal tissues from 36 gastric cancer patients with informed consent in our hospital, the study was approved by our patients. The human gastric epithelial cell line GES-1, and gastric cancer cell lines (GTL-16, AGS, HGC-27, and MKN74) were purchased from ATCC (Manassas, VA, USA). GES-1, MKN74, and GTL-16 cells were maintained in RPMI-1640 medium (Gibco, USA), AGS cells were maintained in F–12K medium (Gibco, USA), and HGC-27 cells were maintained in

The identification of CEMIP and miR-375 in gastric cancer

By analyzing GSE103236 data series, we selected 88 differentially expressed genes (DEGs) using the criteria of adjusted P < 0.05 and logFC>2 (Supplementary Table 1) because we were interested in significantly upregulated genes in gastric cancer. Among the 88 significantly upregulated DEGs, we noticed that the top ranked COL10A1 had been extensively studied in gastric cancer, thus we moved to the second top ranked CEMIP. CEMIP has been found as a significant cancer driver in human cancers, such

Discussion

We found increased CEMIP expression, but decreased miR-148a-3p expression in gastric cancer tissue and cell lines. Overexpression of CEMIP promoted cellular viability and adhesion, whereas hampered cell apoptosis. Furthermore, miR-148a-3p mimic treatment could attenuate cell growth and enhance cell apoptosis in gastric cancer. Importantly, miR-148a-3p repressed the progression of gastric cancer via inhibiting CEMIP.

During the past decade, the role of CEMIP has been clarified in various cancers [

Conclusion

Overall, we uncovered that miR-148a-3p inhibited CEMIP level to attenuate the progression of gastric cancer, which may provide new direction for the therapy of gastric cancer.

Declaration of competing interest

The authors declare that they have no conflict of interests.

Acknowledgements

None.

References (28)

  • Y. Chen et al.

    Cell migration inducing hyaluronidase 1 (CEMIP) activates STAT3 pathway to facilitate cell proliferation and migration in breast cancer

    J. Recept. Signal Transduct. Res.

    (2021)
  • R. Hu et al.

    Long non-coding RNA HCP5 promotes prostate cancer cell proliferation by acting as the sponge of miR-4656 to modulate CEMIP expression

    Oncol. Rep.

    (2020)
  • E. Hornstein et al.

    The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development

    Nature

    (2005)
  • M. Boehm et al.

    MicroRNA control of lifespan and metabolism

    Cell Cycle

    (2006)
  • Cited by (0)

    1

    The authors contribute equally to this work.

    View full text