Construction of PARPi Resistance-related Competing Endogenous RNA Network

Lili Kong1, Jiaqi Xu2,3, Lijun Yu1

  • 1Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China.

Current Genomics
|February 13, 2023
PubMed

Insights

Poly (ADP-ribose) polymerase inhibitors (PARPi) resistance in ovarian cancer is a challenge. This study identified key RNA networks and pathways, revealing potential new targets for overcoming PARPi resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Ovarian cancer is a common gynecological malignancy.
  • Poly (ADP-ribose) polymerase inhibitors (PARPi) are used for treatment, but resistance limits their efficacy.
  • Mechanisms underlying PARPi resistance require further elucidation.

Purpose of the Study:

  • To characterize RNA expression profiles and construct regulatory networks in PARPi-resistant ovarian cancer cells.
  • To identify key regulatory ceRNA axes and their involved pathways in PARPi resistance.
  • To provide insights for developing novel therapeutic targets against PARPi resistance.

Main Methods:

  • RNA sequencing was performed on PARPi (Olaparib)-induced ovarian cancer cells.
  • Differential expression analysis of mRNAs, lncRNAs, circRNAs, and miRNAs was conducted.
  • RNA regulatory networks, particularly ceRNA networks, were constructed and analyzed.

Main Results:

  • Differentially expressed genes were enriched in PI3K/AKT, MAPK signaling, and metabolic pathways.
  • Key regulatory ceRNA axes involving lncRNAs, circRNAs, miRNAs, and mRNAs were identified.
  • miR-320b was identified as a crucial mediator in these regulatory networks.

Conclusions:

  • Key regulatory lncRNA-circRNA-miRNA-mRNA axes and their associated pathways were revealed in PARPi-resistant ovarian cancer.
  • These findings offer new perspectives on ceRNA regulatory networks in drug resistance.
  • The identified axes and pathways represent potential targets for overcoming PARPi resistance in ovarian cancer.

Related Concept Videos

piRNA - Piwi-interacting RNAs02:57

piRNA - Piwi-interacting RNAs

PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
7.0K
RNA Interference01:23

RNA Interference

RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
26.2K
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...
6.2K
siRNA - Small Interfering RNAs02:30

siRNA - Small Interfering RNAs

Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
16.9K
Riboswitches01:56

Riboswitches

Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
8.2K
RACE - Rapid Amplification of cDNA Ends02:35

RACE - Rapid Amplification of cDNA Ends

Rapid Amplification of cDNA Ends, or RACE, is one of the most effective methods to obtain a full-length cDNA from an mRNA sequence between a known internal region to the unknown sequence at the 5’ or 3’ end. The unknown region is cloned in the cDNA by a gene-specific primer that binds the known end, and a hybrid primer that attaches a predefined anchor sequence to the unknown end of the cDNA. The sequence in between is amplified by PCR with an anchor primer and a gene-specific...
6.4K