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CasRx-Based KRASG12D Silencing for In Vivo Tumor Inhibition in Spontaneous Lung Adenocarcinoma

GSE252971 Mus musculus (mouse) RNA-seq (gene expression) 28 samples Submitted 2024/12/31 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 28 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
28 samples: 8 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
Lung adenocarcinoma with KRAS mutation represents a formidable challenge in cancer treatment due to its undruggable oncogenic mutation. Here, we explored the CasRx-editing approach on lung adenocarcinoma driven by the KRAS activation and Tp53 loss in vivo, a scenario closely resembling clinical conditions. We screened seven sgRNAs in cultured cells and identified that CasRx combined with sgRNA5 effectively suppressed murine KRASG12D transcript levels by 93.185 ± 4.758%, leading to significant attenuation of cell viability and proliferation.
Read the full summary ↓
Subsequently, we administered CasRx + sgRNA5 via in vivo Adeno-associated viruses (AAV) delivery at the early tumorigenesis stage, resulting in inhibition of tumor initiation and progression, ultimately enhancing the survival of the mice. Mechanistically, the treatment directly targeted the classic KRAS signal pathways and regulated a potential protein network comprising KRAS, DUSP8, NR4A1, DUSP1, and EGR1. Encouragingly, the CasRx + sgRNA5 treatment in mice bearing the induced lung adenocarcinoma demonstrated an optimistic therapeutic outcome, characterized by reduced mutation burden, diminished tumor size, and seemingly improved overall survival. Remarkably, no obvious off-target events were detected in the treated tissues, highlighting the specificity and safety of CasRx + sgRNA5 therapy. This study establishes the feasibility of CasRx-based-KRASG12D editing for efficient in vivo tumor inhibition and provides insights into the potential role of the KRAS-associated protein network in the early development of lung cancer. These findings hold great promise for the development of novel targeted therapies for this aggressive malignancy.
This dataset
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE252971_RAW.tar (it can run to tens of gigabytes).

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1063353 and SRA study SRP482974. Searching any of these in the dataset finder brings you back here.

Study design
8 conditions, mostly in triplicate
Lung tissues in strategy2, CasRx + sgNC, 6 wp… ×6 Lung tissues in strategy2, CasRx + sgRNA5, 6 … ×4 Lung tissues in strategy1, CasRx + sgNC, 2 wp… ×3 Lung tissues in strategy1, CasRx + sgRNA2, 2 … ×3 Lung tissues in strategy1, CasRx + sgRNA5, 2 … ×3 Lung tissues in strategy1, CasRx + sgNC, 12 w… ×3 Lung tissues in strategy1, CasRx + sgRNA2, 12… ×3 Lung tissues in strategy1, CasRx + sgRNA5, 12… ×3

Supports a between-group comparison across 28 samples.

How we read this: 8 replicated groups read from 28 sample titles; they account for 28 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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