MIR-147B REGULATED PROLIFERATION
AND APOPTOSIS OF GASTRIC CANCER CELLS
BY TARGETING CPEB2 VIA THE PTEN PATHWAY
Tao K.1,2, Dong J-H.2, Wang D.1, Li F.2†#, Zhang Z-T.#1*
*Corresponding Author: Zhong-Tao Zhang, MD, Email: sxzhangzhongtao@sina.com, ORCID ID: 0000-0002-1184-2591
#: Zhong-Tao Zhang and Feng Li contributed equally to the article
†: Co-corresponding author: Feng Li, Email: sxlifengwobuxin@sina.com, ORCID: 0000-0002-7322-422X
page: 10
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DISCUSSION
MicroRNA (miRNA), a well-known noncoding RNA
subtype has recently appeared as gene expression regulators
by combining its target messenger 3 ʹ- Non translation
area (3ʹ- UTR) which transcriptionally regulates the
gene expression of the messenger RNA (mRNA) 11. The
interaction of miRNA and mRNA generate RNA and induce
a silencing complex, which is an event promoting
mRNA degradation and translation inhibition 11. Therefore,
miRNA is believed to promote tumorigenesis 12,13. Various
studies have suggested that numerous miRNAs disorders
are involved in regulating tumor malignant growth and
invasive metastasis; therefore, they act as oncogenes or
tumor suppressors 14,15. In addition, itis used significantly
as a biomarker, in prognosis, as well as a therapeutic target
16,17. miR-147b has been also associated with a variety of
cancers 18–20.
In this study, differentially expressed miRNAs were
screened from 3 pairs of samples by miRNA chip. The
cut-off point of multiple changes was 1.50 or 0.67. An
miRNA microarray detected that the concentration of 14
miRNAs in GC tissues was up-regulated, among which
hsa-miR-147b was more significant. Further extraction of
miR-147b in gastric cancer tissues was established as extensively
elevated when compared to neighboring tissues,
thus confirming that miR-147b was highly expressed in
gastric cancer tissues. miR-147b was also highly expressed
in GC cell lines. Our further functional assay showed that
the addition of miR-147b inhibitor considerably repressed
the propagation and incursion of gastric cancer cells.
Similarly, miR-147b is up-regulated in hepatitis-C
virus related diffuse large B-cell lymphoma, and patients
with elevated miR-147b usually have a low prognosis17.
In addition, the expression of miR-147b increased abnormally
in hepatocellular carcinoma tissues. This was related
to tumor severity, and also thus promoted the growth of
hepatocellular carcinoma in vitro 19. These findings support
the carcinogenic effect of miR-147b. These results
are consistent with this study, but it was also found that
the addition of exogenous miR-147b inhibitor does not
significantly inhibit viability and incursion of gastric cancer
cells in in vitro, indicating that there are other related
microRNAs at the same time.
On the contrary, some studies have shown that miR-
147b is found to be reduced in tumor samples and functions
as a tumor suppressor. The level of miR-147b expression
was found low in rectal cancer tissues and reduce the
propagation and incursion of colorectal cancer cells 19,20.
miR-147b can be used as a protecting predictive indicator
in patients with ovarian cancer 16, where its function may
vary from tumor to tumor 21. Therefore, the exact role of
miR-147b in tumorigenesis needs to be further studied in
different tumor types.
The gene silencing, and the abnormal expression of
downstream genes in tumor tissues may be caused by
dysregulated miRNA. It promotes or inhibits eukaryotic
mRNA translation by engaging the dynamic change of
poly (A) tail length in cytoplasm 22. In the cytoplasm, the
lengthening or shortening of poly (A) is arbitrated by the
interaction of the cytoplasmic polyadenylation element
(CPE, a cis factor) and RNA binding protein (CPEB, a
trans factor). This phenomenon is called cytoplasmic polyadenylation
by CPEB protein 23. CPEB2, a member of the
CPEB protein family is found concentrated in cytoplasm
during transfection and connects to poly (U) RNA oligomers
24. It functions as a translation regulator. In the human
genome database, it was found that theCPEB2 nucleotide
sequence was a potential target gene of miR-147b in gastric
cancer, which was confirmed by luciferase experiment.
Western blotting showed that miR-147b negatively regulated
CPEB2 and then affected the expression of the PTEN
protein. The results of the study suggest that the expression
of CPEB2 was not considerably associated with gender,
age, tumor location, tumor size and histological type, but
with tumor cell differentiation, TNM stage and lymph node
metastasis. The lower the expression of CPEB2, the worse the tumor differentiation, accompanied by the increase of
TNM stage and the aggravation of lymph node metastasis
load. Patients with high expression of miR-147b and low
expression of CPEB2 had poor 5-year overall survival.
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