LncRNA SNHG12 Decreases Non-Small Cell Lung Cancer Cell Sensitivity to Cisplatin by Repressing miR-525-5p and

Deli Tan1, Song Wang1, Peng Zhang1

  • 1Department of Thoracic Surgery, Southwest Hospital, Chongqing Ninth People's Hospital, Chongqing, China.

Abstract

Insights

Long noncoding RNA SNHG12 promotes cisplatin resistance in non-small cell lung cancer by upregulating XIAP via inhibiting miR-525-5p. This finding offers potential therapeutic targets for overcoming drug resistance in NSCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality worldwide.
  • Long noncoding RNAs (lncRNAs) play a role in NSCLC progression and drug resistance.
  • Understanding the mechanisms of cisplatin resistance is crucial for improving NSCLC treatment outcomes.

Purpose of the Study:

  • To investigate the role of lncRNA SNHG12 in cisplatin (DDP) resistance in NSCLC cells.
  • To elucidate the underlying molecular mechanism involving miR-525-5p and XIAP.
  • To explore potential therapeutic strategies targeting the SNHG12/miR-525-5p/XIAP axis.

Main Methods:

  • Quantitative reverse-transcription polymerase chain reaction (RT-qPCR) to measure gene expression.
  • Cell counting kit-8 (CCK-8), colony formation, and flow cytometry assays to assess cell viability, proliferation, and apoptosis.
  • Transfection of small interfering RNAs (siRNAs), microRNA inhibitors, and plasmids.
  • Dual-luciferase reporter gene assays to confirm binding interactions.
  • Nuclear/cytosol fractionation to determine subcellular localization.

Main Results:

  • SNHG12 and XIAP were upregulated, while miR-525-5p was downregulated in NSCLC cells.
  • SNHG12 knockdown enhanced DDP sensitivity by increasing apoptosis and decreasing proliferation.
  • SNHG12 directly repressed miR-525-5p, which in turn targeted and inhibited XIAP.
  • Overexpression of XIAP or inhibition of miR-525-5p conferred DDP resistance.

Conclusions:

  • SNHG12 promotes DDP resistance in NSCLC by upregulating XIAP through the repression of miR-525-5p.
  • The SNHG12/miR-525-5p/XIAP axis is a key regulator of DDP resistance in NSCLC.
  • Targeting this axis may represent a promising therapeutic strategy for overcoming DDP resistance in NSCLC.

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...
8.7K
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...
3.1K
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
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
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
Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.3K