MiR-4766-5p Inhibits The Development And Progression Of Gastric Cancer By Targeting NKAP

Our plain-English summary of MiR-4766-5p Inhibits The Development And Progression Of Gastric Cancer By Targeting NKAP, by Y. Wei, Y. Wang, A. Zang, et al (OncoTargets and Therapy, 2019).

The study

• Authors: Y. Wei, Y. Wang, A. Zang, Z. Wang, G. Fang, D. Hong
• Journal: OncoTargets and Therapy
• Published: 2019;12:8525-8536
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Purpose: It is widely known that some specific microRNAs can regulate the expressions of genes in gastric cancer cells at the post-transcriptional level. Previous studies have identified that miRNA-4766-5p was involved in tumor cell proliferation and can be an independent prognostic indicator for malignant pleural mesothelioma. However, the mechanism underlying gastric cancer via the miRNA-4766-5p pathway remains to be blank.

Methods: We investigated the expression of miR-4766-5p in gastric cancer tissues and cells through qRT-PCR. We used RNAi to change the expressions of miR-4766-5p in gastric cancer cell lines, AGS and MKN45. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the mRNA expression of miR-4766-5p. We identified cell proliferation by CCK8 and clone formation assays. We analyzed the cell apoptosis and cycle through flow cytometry. At last, we used a dual-luciferase reporter assay to illustrate the interaction between miR-4766-5p and NKAP and used Western blot to determine the protein expression of signaling pathways.

Results: We found that 1) miR-4766-5p was down-regulated in gastric cancer tissues and cells lines; 2) miR-4766-5p inhibited cell proliferation of gastric cancer cell lines significantly; 3) miR-4766-5p significantly inhibited cell migration and invasion of gastric cancer cells; 4) miR-4766-5p induced gastric cancer cell apoptosis. 5) NKAP was a direct target gene of miR-4766-5p; and 6) miR-4766-5p induced inactivation of AKT/mTOR pathway.

Conclusion: The above results indicate that miR-4766-5p suppressed the proliferation and metastasis of gastric cancer cells through targeting NKAP. Our findings could probably contribute to the diagnostics and prognostics of gastric cancer through new methodologies.

© 2019 Wei et al.

In plain English

This laboratory study was about stomach (gastric) cancer, not asbestos. Its only mention of mesothelioma is an opening line saying earlier studies found miR-4766-5p can be an independent prognostic indicator (a predictor of patient outcome) for malignant pleural mesothelioma. The article gives no reference for it and does not test it. The authors measured miR-4766-5p in tumor and nearby normal tissue from 30 surgery patients, and in cell lines. They then raised or lowered its level in two gastric cancer cell lines, AGS and MKN45. In mice, they implanted AGS cells altered to overproduce miR-4766-5p, or control cells, with 6 mice per group. They reported that miR-4766-5p was significantly lower in cancer tissue than in nearby normal tissue. In cells, it was linked to fewer colonies, less migration and invasion, more cell death, lower NKAP protein, and reduced AKT/mTOR activity. Tumors from cells with raised miR-4766-5p grew significantly more slowly than control tumors. Measured values appear only in figures; the text gives P-value thresholds. The authors concluded that miR-4766-5p suppressed gastric cancer cell growth and spread by targeting NKAP.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study using human gastric cancer tissue samples, cell lines, and a mouse xenograft (tumor implant) experiment
• Who was studied: Paired gastric cancer and adjacent normal tissues from 30 patients undergoing radical surgery at the Affiliated Hospital of Hebei University, China, July 2010 to February 2015. Also studied: gastric cancer cell lines (MGC-803, AGS, MKN45, SGC-790), a normal gastric epithelial cell line (GES-1), and female BALB/c nude mice (n=6 per group).
• Exposure: No asbestos or fiber exposure was studied. In cultured cells, the authors raised (overexpression plasmid, mimics) or lowered (siRNA) levels of the microRNA miR-4766-5p. In mice, they implanted only AGS cells transfected to overexpress miR-4766-5p, or control-vector cells.
• Main results:
  • In the 30 patients, miR-4766-5p was significantly lower in gastric cancer tissue than in adjacent normal tissue (the figure legend gives P<0.001).
  • Among the cell lines, AGS and MKN45 cells showed the lowest miR-4766-5p expression.
  • In AGS and MKN45 cells, miR-4766-5p reduced colony numbers. The authors interpreted this as a negative role in cell proliferation.
  • Lowering miR-4766-5p significantly increased migration and invasion of AGS and MKN45 cells.
  • miR-4766-5p significantly increased the percentage of apoptotic (programmed-death) gastric cancer cells.
  • Overexpressing miR-4766-5p reduced NKAP protein, and miR-4766-5p expression was negatively correlated with NKAP expression.
  • In gastric cancer cells, miR-4766-5p significantly lowered phosphorylated AKT and mTOR.
  • In nude mice implanted with AGS cells, overexpressing miR-4766-5p significantly inhibited tumor growth compared with the control vector group (P<0.05).
• The authors' conclusion: The authors concluded that miR-4766-5p suppressed proliferation and metastasis of gastric cancer cells by targeting NKAP and inhibiting the AKT/mTOR signaling pathway.

Topics

Medical terms in this study, explained in our Lexicon: Stomach Cancer, Pleural Mesothelioma, Apoptosis, Metastasis.

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