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MicroRNA-132-3p inhibits tumor malignant progression by regulating lysosomal-associated protein transmembrane 4 beta

Sha Li1, Jian-Jun Xu1, Qing-Yun Zhang1

  • 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Clinical Laboratory, Peking University Cancer Hospital & Institute, Beijing, China.

Cancer Science
|August 8, 2019
PubMed

Insights

MicroRNA-132-3p (miR-132-3p) directly targets and downregulates the proto-oncogene LAPTM4B, suppressing breast cancer progression and metastasis. Low miR-132-3p levels indicate poor prognosis and potential for recurrence in breast cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Lysosomal-associated protein transmembrane 4 beta (LAPTM4B) is a proto-oncogene that promotes cancer progression.
  • The regulatory mechanisms of LAPTM4B, particularly involving microRNAs (miRNAs), are not fully understood in breast cancer.
  • Aberrant miRNA expression is implicated in breast cancer development and progression.

Purpose of the Study:

  • To investigate the regulatory role of miR-132-3p in breast cancer.
  • To elucidate the relationship between miR-132-3p and LAPTM4B expression and function.
  • To evaluate the diagnostic and prognostic value of miR-132-3p in breast cancer.

Main Methods:

  • Bioinformatic prediction of miRNA targets.
  • Luciferase reporter assays to confirm direct binding of miR-132-3p to LAPTM4B 3'UTR.
  • Western blot analysis to assess protein expression levels.
  • Analysis of clinical breast cancer tissues for miR-132-3p and LAPTM4B expression.
  • Receiver-operating characteristic (ROC) curve analysis, Kaplan-Meier, and Cox regression models for diagnostic and prognostic evaluation.
  • In vitro cell migration, invasion, and epithelial-mesenchymal transition (EMT) assays.
  • Investigation of the PI3K-AKT-mTOR signaling pathway.

Main Results:

  • miR-132-3p directly binds to the 3'UTR of LAPTM4B and negatively regulates its expression.
  • miR-132-3p is significantly downregulated in breast cancer tissues and inversely correlated with LAPTM4B expression.
  • Low miR-132-3p levels are associated with accurate diagnosis and serve as a potential prognostic marker for breast cancer recurrence.
  • miR-132-3p suppresses breast carcinoma cell migration and invasion by modulating EMT signals via LAPTM4B.
  • miR-132-3p partially reverses LAPTM4B's oncogenic effects by inhibiting the PI3K-AKT-mTOR pathway.

Conclusions:

  • miR-132-3p acts as a direct tumor suppressor miRNA targeting LAPTM4B in breast cancer.
  • The miR-132-3p/LAPTM4B axis plays a critical role in breast cancer oncogenesis and metastasis.
  • miR-132-3p holds potential as a diagnostic biomarker and therapeutic target for breast cancer.
Keywords:
LAPTM4Bbreast cancermetastasismiR-132-3pregulation

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