miR-548b-3p functions as a tumor suppressor in lung cancer

Zhenlin Wang1, Xingfu Wu2, Xiangwei Hou2

  • 1Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road Shanghai, Shanghai, China.

Lasers in Medical Science
|September 6, 2019
PubMed

Insights

MicroRNA-548b-3p (miR-548b-3p) is downregulated in lung cancer. This microRNA inhibits tumor growth and promotes apoptosis, suggesting its potential as a future anti-lung cancer therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The miR-548 family, a primate-specific microRNA gene family, has members with largely uncharacterized roles in human diseases.
  • The specific function of microRNA-548b-3p (miR-548b-3p) in the context of lung cancer pathogenesis remains poorly understood.
  • Investigating novel microRNAs like miR-548b-3p is crucial for identifying new therapeutic strategies against lung cancer.

Purpose of the Study:

  • To investigate the expression levels of miR-548b-3p in lung cancer tissues and cell lines.
  • To determine the functional role of miR-548b-3p in regulating lung cancer cell proliferation and apoptosis.
  • To elucidate the molecular mechanisms underlying miR-548b-3p's effects on lung cancer, including its potential impact on signaling pathways.

Main Methods:

  • Quantitative real-time PCR was used to assess miR-548b-3p expression in clinical lung tumor specimens and human lung cancer cell lines compared to normal controls.
  • In vitro cell-based assays were performed to evaluate the effects of miR-548b-3p on lung cancer cell proliferation and apoptosis, including cell cycle analysis.
  • Western blotting was employed to examine the modulation of key proteins within the PI3K/AKT signaling pathway.
  • In vivo tumor growth was assessed using a xenograft mouse model implanted with lung cancer cells engineered to express miR-548b-3p.

Main Results:

  • Expression of miR-548b-3p was significantly reduced in both lung tumor tissues and lung cancer cell lines relative to normal counterparts.
  • Overexpression of miR-548b-3p in vitro led to the inhibition of lung cancer cell proliferation and induced apoptosis, particularly during the S phase of the cell cycle.
  • The observed anti-proliferative and pro-apoptotic effects of miR-548b-3p were associated with the downregulation of the PI3K/AKT signaling pathway.
  • In vivo studies demonstrated that miR-548b-3p suppressed tumor growth in a xenograft mouse model, confirming its anti-tumorigenic potential.

Conclusions:

  • miR-548b-3p exhibits tumor-suppressive properties in lung cancer, acting as an inhibitor of cell proliferation and a promoter of apoptosis.
  • The anti-cancer effects of miR-548b-3p are mechanistically linked to the inhibition of the PI3K/AKT signaling pathway.
  • These findings highlight miR-548b-3p as a promising candidate for future development as a targeted therapeutic agent against lung cancer.

Related Concept Videos

Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.9K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.4K
Non-Invasive Ultrasound Assessment of Endometrial Cancer Progression in Pax8-Directed Deletion of the Tumor Suppressors Arid1a and Pten in Mice07:44

Non-Invasive Ultrasound Assessment of Endometrial Cancer Progression in Pax8-Directed Deletion of the Tumor Suppressors Arid1a and Pten in Mice

This protocol describes a method for monitoring the progression of morphological changes over time in the uterus in an inducible mouse model of endometrial cancer using ultrasound imaging with correlation to gross and histological...
2.0K
Tracking Tumor Cell Dissemination from Lung Metastases Using Photoconversion05:23

Tracking Tumor Cell Dissemination from Lung Metastases Using Photoconversion

We present a method for studying tumor cell redissemination from lung metastases involving a surgical protocol for the selective photoconversion of lung metastases, followed by the identification of redisseminated tumor cells in tertiary...
1.6K
Using Micro-computed Tomography for the Assessment of Tumor Development and Follow-up of Response to Treatment in a Mouse Model of Lung Cancer11:31

Using Micro-computed Tomography for the Assessment of Tumor Development and Follow-up of Response to Treatment in a Mouse Model of Lung Cancer

We describe a method for the detection of tumor nodule development in the lungs of an adenocarcinoma mouse model using micro-computed tomography and its use for monitoring changes in nodule size over time and in response to treatment. The accuracy of the assessment was confirmed with end-point histological...
11.2K
Detection of Lung Tumor Progression in Mice by Ultrasound Imaging04:43

Detection of Lung Tumor Progression in Mice by Ultrasound Imaging

This protocol describes the steps taken to induce KRAS lung tumors in mice as well as the quantification of formed tumors by ultrasound imaging. Small tumors are visualized in early timepoints as B-lines. At later timepoints, relative tumor volume measurements are achieved by the measurement tool in the ultrasound...
7.3K