MiR-148a-3p targets CEMIP to suppress the genesis of gastric cancer cells
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.
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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)
- et al.
Anti-silencing function 1B histone chaperone promotes cell proliferation and migration via activation of the AKT pathway in clear cell renal cell carcinoma
Biochem. Biophys. Res. Commun.
(2019) - et al.
CEMIP promotes ovarian cancer development and progression via the PI3K/AKT signaling pathway
Biomed. Pharmacother.
(2019) MicroRNAs: genomics, biogenesis, mechanism, and function
Cell
(2004)- et al.
MicroRNA-148a-3p enhances cisplatin cytotoxicity in gastric cancer through mitochondrial fission induction and cyto-protective autophagy suppression
Canc. Lett.
(2017) - et al.
miR-148a-3p suppresses the proliferation and invasion of esophageal cancer by targeting DNMT1
Genet. Test. Mol. Biomarkers
(2019) - et al.
Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries
CA A Cancer J. Clin.
(2018) - et al.
Dissection of gastric cancer heterogeneity for precision oncology
Canc. Sci.
(2019) - et al.
Identification of candidates for driver oncogenes in scirrhous-type gastric cancer cell lines
Canc. Sci.
(2019) - et al.
A novel metastatic promoter CEMIP and its downstream molecular targets and signaling pathway of cellular migration and invasion in SCLC cells based on proteome analysis
J. Canc. Res. Clin. Oncol.
(2020) - et al.
Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis
Nat. Cell Biol.
(2019)
Cell migration inducing hyaluronidase 1 (CEMIP) activates STAT3 pathway to facilitate cell proliferation and migration in breast cancer
J. Recept. Signal Transduct. Res.
Long non-coding RNA HCP5 promotes prostate cancer cell proliferation by acting as the sponge of miR-4656 to modulate CEMIP expression
Oncol. Rep.
The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development
Nature
MicroRNA control of lifespan and metabolism
Cell Cycle
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The authors contribute equally to this work.