RGD Reference Report - MicroRNA-222-3p associated with Helicobacter pylori targets HIPK2 to promote cell proliferation, invasion, and inhibits apoptosis in gastric cancer. - Rat Genome Database

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MicroRNA-222-3p associated with Helicobacter pylori targets HIPK2 to promote cell proliferation, invasion, and inhibits apoptosis in gastric cancer.

Authors: Tan, Xiaoyan  Tang, Haiying  Bi, Jian  Li, Na  Jia, Yujie 
Citation: Tan X, etal., J Cell Biochem. 2018 Jul;119(7):5153-5162. doi: 10.1002/jcb.26542. Epub 2018 Mar 25.
RGD ID: 151708731
Pubmed: PMID:29227536   (View Abstract at PubMed)
DOI: DOI:10.1002/jcb.26542   (Journal Full-text)

Gastric cancer ranks as the second leading cause of malignancy-related death worldwide, and always diagnosed at advanced stage. MicroRNA-222-3p (miR-222-3p) is aberrantly upregulated in various malignant tumors including gastric cancer, but its role and underlying molecular mechanisms in gastric cancer remain largely unknown. Helicobacter pylori (H. pylori) infection acts as a trigger in the development of gastric cancer, and increasing evidence suggests that H. pylori affects microRNA expression. In this study, gastric cancer tissue samples were divided into H. pylori positive group (+) and negative group (-). QRT-PCR showed that miR-222-3p was significantly upregulated in H. pylori (+) group compared with H. pylori (-) group, and luciferase reporter assays identified homeodomain-interacting protein kinase 2 (HIPK2) as a novel target of miR-222-3p in gastric cancer. Immunohistochemistry revealed that HIPK2 levels were decreased in H. pylori (+) group compared with H. pylori (-). After that, functional experiments indicated that miR-222-3p overexpression promoted the proliferation and invasion, while inhibiting apoptosis of SGC7901 gastric cancer cells, but miR-222-3p knockdown exhibited the opposite effects. Also, HIPK2 knockdown induced similar effects as miR-222-3p overexpression in SGC7901 cells. Nude mouse experiments further suggested that HIPK2 overexpression signally attenuated the enhancing effect of miR-222-3p overexpression on cell proliferation, indicating that the effect of miR-222-3p on gastric cancer progression depends on HIPK2, at least in part. Overall, our results demonstrated that miR-222-3p/HIPK2 signal pathway regulated gastric cancer cell proliferation, apoptosis, and invasion, provided a novel therapeutic target for the treatment of gastric cancer infected by H. pylori.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Helicobacter Infections  IEP 151708731associated with stomach cancer and RNA:increased expression:stomach:RGD 
Helicobacter Infections  ISOMIR222 (Homo sapiens)151708731; 151708731associated with stomach cancer and RNA:increased expression:stomach:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mir222  (microRNA 222)

Genes (Mus musculus)
Mir222  (microRNA 222)

Genes (Homo sapiens)
MIR222  (microRNA 222)


Additional Information