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The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
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The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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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...
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Related Experiment Video

Updated: Jan 13, 2026

HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries
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THOC1 complexes with SIN3A to regulate R-loops and promote glioblastoma progression.

Shreya Budhiraja1, Umme H Faisal2, Shivani Baisiwala2

  • 1Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, USA; Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, USA.

Neoplasia (New York, N.Y.)
|January 7, 2026
PubMed
Summary

Targeting THO Complex 1 (THOC1) is a promising strategy for glioblastoma (GBM). Reducing THOC1 disrupts R-loops, hindering GBM cell replication and improving survival in models.

Keywords:
Genome-wide CRISPR screenGlioblastomaProgressionR-loopsTHOC1

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis.
  • Identifying novel therapeutic targets is crucial for improving GBM patient survival.

Purpose of the Study:

  • To identify key drivers of glioblastoma pathogenesis using a CRISPR-knockout screen.
  • To investigate the role of THO Complex 1 (THOC1) in GBM development and progression.

Main Methods:

  • CRISPR-knockout screening in patient-derived xenograft (PDX) models.
  • Assessment of cell viability, survival, and tumor engraftment.
  • RNA-sequencing and analysis of R-loop levels and histone deacetylation.

Main Results:

  • THO Complex 1 (THOC1) was identified as a key driver of GBM.
  • Knockdown of THOC1 reduced GBM cell viability and enhanced survival in PDX models.
  • THOC1 knockdown led to increased R-loop levels, reduced histone deacetylation, and telomere shortening, particularly at telomeres.

Conclusions:

  • THOC1 plays a critical role in maintaining the R-loop landscape essential for GBM cell replication.
  • Targeting THOC1 is a potential therapeutic strategy to disrupt GBM's replicative potential and improve outcomes.