SLC39A7, regulated by miR-139-5p, induces cell proliferation, migration and inhibits apoptosis in gastric cancer via Akt/mTOR signaling pathway - PubMed (original) (raw)

SLC39A7, regulated by miR-139-5p, induces cell proliferation, migration and inhibits apoptosis in gastric cancer via Akt/mTOR signaling pathway

Yanting Zhang et al. Biosci Rep. 2020.

Abstract

As a zinc transporter, SLC39A7 (zip7) is vital in intestinal epithelial self-renewal, and recent studies suggested that SLC39A7 was related to cancer progression. Whereas, little is known about the role of SLC39A7 in gastric cancer (GC). In the present study, qRT-PCR analysis demonstrated that SLC39A7 mRNA level was increased in both GC tissues and cell lines. Overexpressing SLC39A7 boosted cell proliferation and migration, while inhibited apoptosis in GC. It was also found that si-SLC39A7 suppressed Akt/mTOR pathway and activation of Akt/mTOR pathway reversed the effects of si-SLC39A7 on GC development. Through prediction website, we found that SLC39A7 was directly regulated by miR-139-5p. miR-139-5p mimic had adverse effects on SLC39A7 expression and influence in the GC cell proliferation, migration and apoptosis by Akt/mTOR signaling pathway, while miR-139-5p inhibitor showed opposite effects. To conclude, our studies showed that SLC39A7 was negatively regulated by miR-139-5p. Besides, SLC39A7 positively regulated GC development through Akt/mTOR signaling pathway. These results indicate that SLC39A7 may be a candidate target gene for GC treatment.

Keywords: SLC39A7; gastric cancer; miR-139-5p; proliferation.

© 2020 The Author(s).

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1

Figure 1. SLC39A7 is highly expressed in GC

(A) qRT-PCR was used to detect SLC39A7 mRNA expression in GC tissues. (B) SLC39A7 mRNA and (C) protein level in GC cells were analyzed via qRT-PCR and Western blot. **P<0.01 vs normal tissues or GES-1 cells.

Figure 2

Figure 2. SLC39A7 promoted GC cell proliferation and migration while inhibiting cell apoptosis

MGC-803 and HGC-27 cells were cultured and transfected with si-RNA, si-SLC39A7, pcDNA3.1 or pcDNA3.1-SCL39A7. (A–C) Transfection efficiency of pcDNA3.1-SLC39A7 and si-SLC39A7 were evaluated by qRT-PCR and Western blot. (D,E) Cell proliferation and migration were evaluated by MTT assay and wound-healing assay. (F) Cell apoptosis was evaluated by apoptosis analysis. **P<0.01 vs pcDNA3.1 and ##P<0.01 vs si-RNA.

Figure 3

Figure 3. SLC39A7 affects GC cells proliferation, migration and apoptosis through Akt/mTOR pathway

HGC-27 cells were transfected with si-RNA or si-SLC39A7 and treated with SC79 or MHY1485. pS473-Akt/Akt (A,C) and p-mTOR/mTOR (B,C) protein expression in HGC-27 cells was assessed by Western blot. (D) MTT assay, (E) wound-healing assay and (F) apoptosis assay were recruited to analyze the proliferation, migration and apoptosis of HGC-27 cells with si-SLC39A7 or si-RNA transfection and SC79 or MHY1485 treatment. ##P<0.01 vs si-RNA and &&P<0.01 vs si-SLC39A7.

Figure 4

Figure 4. miR-139-5p targets SLC39A7 directly

(A) The putative binding sequence of miR-139-5p in wild-type and mutant SLC39A7-3′UTR. (B) The relative luciferase activity with wild-type or mutant SLC39A7-3′UTR in HGC-27 cells transfected with the miR-139-5p or miR-NC were analyzed. (C) qRT-PCR was applied to assess SLC39A7 mRNA expression in miR-139-5p or miR-139-5p inhibitor transfected group and respective NC group. (D,E) mRNA levels of miR-139-5p in gastric tissues and cell lines were detected via qRT-PCR. (F) Spearman’s correlation analysis was recruited to explore the correlation between miR-139-5p and SLC39A7 mRNA level. **P<0.01 vs miR-139-5p and ##P<0.01 vs miR-139-5p inhibitor.

Figure 5

Figure 5. SLC39A7 mediated-Akt/mTOR pathway is involved in the miR-139-5p regulated cell proliferation, migration and apoptosis of GC

HGC-27 cells were co-transfected with mimic inhibitor or miR-139-5p mimic and pcDNA3.1 or pcDNA3.1-SLC39A7 with SC79 or MHY1485 treatment. (A–C) The protein expression of pS473-Akt and p-mTOR was evaluated by Western blot. The cell proliferation (D), migration (E) and apoptosis (F) were analyzed via MTT assay, wound-healing assay and apoptosis assay. **P<0.01 vs mimic NC, ##P<0.01 vs miR-139-5p or miR-139-5p + pcDNA-3.1.

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