Related Experiment Video

Updated: Dec 17, 2025

Using an Automated Cell Counter to Simplify Gene Expression Studies: siRNA Knockdown of IL-4 Dependent Gene Expression in Namalwa Cells
10:34

Using an Automated Cell Counter to Simplify Gene Expression Studies: siRNA Knockdown of IL-4 Dependent Gene Expression in Namalwa Cells

Published on: April 14, 2010

15.9K

NLRC3 silencing accelerates the invasion of hepatocellular carcinoma cell via IL-6/JAK2/STAT3 pathway activation

Jian-Hua Kang1, Ming-Jie Li1, Pei-Pei Luan2

  • 1Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Cell Biology International
|June 26, 2020
PubMed

Insights

Nucleotide-binding domain, leucine-rich repeat family with a caspase activation and recruitment domain 3 (NLRC3) is reduced in hepatocellular carcinoma (HCC). Silencing NLRC3 promotes HCC cell growth and invasion via the JAK2/STAT3 pathway, suggesting NLRC3 as a potential therapeutic target.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Nucleotide-binding domain, leucine-rich repeat family with a caspase activation and recruitment domain 3 (NLRC3) is implicated in immune responses and cancer development.
  • The specific role and underlying mechanisms of NLRC3 in human hepatocellular carcinoma (HCC) remain to be fully elucidated.

Purpose of the Study:

  • To investigate the expression patterns of NLRC3 in human HCC tissues.
  • To determine the functional role of NLRC3 in HCC cell proliferation, migration, invasion, and apoptosis.
  • To elucidate the molecular mechanisms by which NLRC3 influences HCC progression, particularly the involvement of the JAK2/STAT3 pathway.

Main Methods:

  • NLRC3 expression was analyzed in human liver tissues (HCC, NASH, normal) using real-time quantitative PCR and immunohistochemistry.
  • HCC cell line (HuH-7) was used to assess the effects of NLRC3 knockdown via small interfering RNA (siRNA).
  • Cell proliferation, migration, invasion, and apoptosis were evaluated using EdU, scratch, Transwell, flow cytometry, and TUNEL assays, respectively.
  • The JAK2/STAT3 pathway activation under IL-6 stimulation was assessed following NLRC3 knockdown, with STAT3 inhibition using cryptotanshinone.

Main Results:

  • NLRC3 expression was significantly reduced in human HCC tissues compared to normal and NASH liver tissues.
  • NLRC3 knockdown in HuH-7 cells led to increased proliferation, migration, and invasion, and suppressed apoptosis.
  • NLRC3 silencing was associated with enhanced IL-6-induced JAK2/STAT3 pathway activation in HCC cells.
  • Inhibition of STAT3 partially reversed the increased invasion of HuH-7 cells after NLRC3 knockdown.

Conclusions:

  • NLRC3 plays a suppressive role in human hepatocellular carcinoma.
  • Downregulation of NLRC3 promotes HCC progression by enhancing cell proliferation, migration, and invasion, potentially through the activation of the IL-6/JAK2/STAT3 signaling pathway.
  • NLRC3 represents a potential therapeutic target for HCC treatment.
Keywords:
NLRC3STAT3hepatocellular carcinomainnate immunity

More Related Videos

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry10:16

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry

Published on: January 6, 2017

7.6K
Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome07:23

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

8.8K

Related Concept Videos

Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
7.1K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
11.4K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.6K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.1K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
9.7K