lncRNA-NKILA/NF-κB feedback loop modulates laryngeal cancer cell proliferation, invasion, and radioresistance

Tao Yang1, Shisheng Li1, Jiajia Liu1

  • 1Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.

Cancer Medicine
|March 25, 2018
PubMed

Insights

Low expression of NKILA (NF-κB interacting lncRNA) is linked to poor survival in laryngeal cancer. NKILA enhances radiotherapy effectiveness by inhibiting NF-κB activation, offering a potential strategy against radioresistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Radiotherapy Research

Background:

  • Laryngeal cancer is a common malignancy often resistant to radiotherapy.
  • NF-κB interacting lncRNA (NKILA) functions as a tumor suppressor by inhibiting NF-κB activation.
  • Understanding NKILA's role in laryngeal cancer is crucial for improving treatment outcomes.

Purpose of the Study:

  • To investigate the expression levels and prognostic significance of NKILA in laryngeal cancer.
  • To elucidate the mechanism by which NKILA influences laryngeal cancer cell behavior and radiosensitivity.
  • To explore NKILA as a potential therapeutic target for overcoming radioresistance.

Main Methods:

  • Quantitative analysis of NKILA expression in laryngeal cancer tissues.
  • Correlation analysis between NKILA levels and patient overall survival.
  • In vitro studies assessing the effects of NKILA modulation on cancer cell viability, migration, and apoptosis.
  • Investigation of NKILA's interaction with the NF-κB signaling pathway components (IκB, p65) and its role in radiosensitization.

Main Results:

  • NKILA expression was significantly lower in laryngeal cancer tissues compared to normal tissues.
  • Low NKILA expression correlated with shorter overall survival in laryngeal cancer patients.
  • NKILA suppressed laryngeal cancer cell viability and migration while promoting apoptosis.
  • NKILA knockdown reversed the radiosensitizing effect of X-ray radiation by inhibiting the NF-κB pathway.
  • A negative feedback loop exists where NF-κB activates NKILA transcription, and NKILA subsequently inhibits NF-κB activation.

Conclusions:

  • NKILA acts as a tumor suppressor in laryngeal cancer.
  • NKILA sensitizes laryngeal cancer cells to X-ray radiation by inhibiting the NF-κB pathway.
  • NKILA represents a promising therapeutic target for enhancing radiotherapy efficacy and overcoming radioresistance in laryngeal cancer.

Related Concept Videos

Feedback Loops01:01

Feedback Loops

In most cases, excessive hormone production is prevented by negative feedback—a loop that starts with a stimulus inducing the release of a particular substance, like a hormone, to maintain a certain level before triggering a signal that results in a decrease in further release of the hormone.
64.7K
Cell Signaling Feedback Loops01:07

Cell Signaling Feedback Loops

Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
7.4K
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
10.0K
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

3.7K
Positive and Negative Feedback Loops01:18

Positive and Negative Feedback Loops

Animal organs and organ systems constantly adjust to internal and external changes through a process called homeostasis ("steady state"). Examples of these changes include regulation of the level of glucose or calcium in the blood or internal responses to external temperatures. Homeostasis requires  maintaining an internal dynamic equilibrium:
25.5K
Feedback Inhibition00:46

Feedback Inhibition

Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!
57.3K