Related Experiment Video

Updated: May 21, 2025

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
09:40

Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

2.5K

HIF-1α-induced long noncoding RNA LINC02776 promotes drug resistance of ovarian cancer by increasing

Yangjun Wu1,2, Yu Zeng3, Yong Wu1,2

  • 1Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.

Clinical and Translational Medicine
|March 21, 2025
PubMed
Abstract

Insights

The long noncoding RNA LINC02776 drives platinum and PARP inhibitor resistance in ovarian cancer. Targeting LINC02776 can re-sensitize ovarian cancer cells to chemotherapy, offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Chemoresistance to platinum-based chemotherapy and PARP inhibitors (PARPi) is a significant challenge in ovarian cancer (OC) treatment.
  • Understanding the molecular mechanisms underlying chemoresistance is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To identify novel molecular factors contributing to platinum resistance in ovarian cancer.
  • To investigate the functional role of LINC02776 in OC chemoresistance and its underlying mechanisms.

Main Methods:

  • Transcriptome-wide analysis using RNA sequencing (RNA-seq) on platinum-resistant and -sensitive OC tissues.
  • Functional studies in OC cells, mice models, and patient-derived organoid (PDO) models.
  • Mechanistic investigations involving LINC02776, PARP1, and homologous recombination (HR) pathway.

Main Results:

  • LINC02776 was identified as a critical factor in platinum resistance, with elevated expression in resistant OC tissues and serving as an independent prognostic factor.
  • Silencing LINC02776 reduced OC cell proliferation and DNA damage repair, enhancing sensitivity to platinum and PARPi in preclinical models.
  • LINC02776 binds to PARP1, promoting PARylation and homologous recombination restoration, with its transcription induced by HIF-1α in resistant OC.

Conclusions:

  • Targeting LINC02776 presents a promising therapeutic strategy for OC patients resistant to platinum or PARPi.
  • LINC02776 promotes OC cell proliferation and chemoresistance by regulating DNA damage, apoptosis, and the PARP1-mediated HR pathway.
Keywords:
HIF‐1αLINC02776PARP1PARPi resistanceovarian cancerplatinum resistance

More Related Videos

Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer04:20

Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer

Published on: February 9, 2024

854
Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment11:13

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

1.4K

Related Concept Videos

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...
8.4K
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...
6.0K
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...
3.0K
Non-LTR Retrotransposons03:18

Non-LTR Retrotransposons

As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
11.3K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.2K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.7K