Related Experiment Video
Updated: Mar 21, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
Phosphorylated DHX9 inhibited the progression of lung adenocarcinoma by regulating R-loops mediated DNA damage
Lei Wu1, Shengyu Wang2, Xin Diao2
1Department of Medical Records Managerment and Date Center, The First Affiliated Hospital of Xi'an Medical University, China.
Abstract:
ObjectivesWe investigated the interactions among DHX9, phosphorylated DHX9, R-loops, and DNA damage to clarify the mechanism by which phosphorylated DHX9 inhibited lung adenocarcinoma progression.MethodsUsed PC-9 and 2BS cells divided into control, siDHX9, OE-DHX9, siDHX9 + OE-RNase H1, OE-PKA, DHX9-S279A, 6-22 Amide, and DHX9-S279A + OE-RNase H1 groups. Assays included quantitative real-time polymerase chain reaction (qRT-PCR), WB (DHX9, γH2AX, Rad51, pCtIP), EdU/CCK-8 (proliferation), TUNEL/flow cytometry (apoptosis), comet assay (DNA damage), CldU/IdU (replication), DRIP-qPCR (R-loops). Nude mice xenografts (control, siDHX9, DHX9-S279E, DHX9-S279A) assessed tumor growth, Ki67, R-loops, DNA damage, and replication.ResultsDHX9 was highly expressed in multiple cancer tissues and lung cancer cell lines, with higher messenger RNA levels in PC-9 than in 2BS cells. Compared with PC-9, siDHX9 reduced proliferation and increased apoptosis, while OE-DHX9 exerted opposite effects. siDHX9 increased DNA damage (with corresponding changes in γH2AX, Rad51, and pCtIP levels), reduced replication (rescued by OE-RNase H1), and elevated R-loops; OE-DHX9 showed opposite effects on damage and R-loops. OE-PKA increased R-loops and damage, and reduced replication, while DHX9-S279A or 6-22 Amide decreased these and 6-22 Amide also increased replication versus PC-9/OE-PKA. DHX9-S279A increased proliferation, with DHX9-S279A + OE-RNase H1 further enhancing this and reducing apoptosis. In vivo, siDHX9 and DHX9-S279E reduced tumor volume/mass and Ki67, increased R-loops, damage, and γH2AX/Rad51/pCtIP, and inhibited replication; DHX9-S279A showed opposite effects versus these groups, with no significant tumor difference versus PC-9 and higher replication versus both.ConclusionsPhosphorylated DHX9 might enhance DNA damage by suppressing R-loop resolution, ultimately inhibiting the proliferation of lung adenocarcinoma cells.
Insights
Phosphorylated DHX9 inhibits lung adenocarcinoma by increasing DNA damage and R-loops, suppressing cell proliferation. This mechanism involves DHX9
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- DHX9 is implicated in cancer progression.
- The role of phosphorylated DHX9 in lung adenocarcinoma is unclear.
- Understanding DHX9's interactions with R-loops and DNA damage is crucial.
Purpose of the Study:
- To investigate the mechanism by which phosphorylated DHX9 inhibits lung adenocarcinoma.
- To elucidate the interplay between DHX9, phosphorylated DHX9, R-loops, and DNA damage.
- To assess the impact of DHX9 modulation on lung cancer cell behavior.
Main Methods:
- Utilized various cell lines (PC-9, 2BS) with genetic manipulations (siDHX9, OE-DHX9, OE-PKA, specific mutants).
- Employed molecular biology techniques: qRT-PCR, Western Blot (WB), EdU/CCK-8, TUNEL, flow cytometry, comet assay, CldU/IdU, and DRIP-qPCR.
- Validated findings in nude mice xenograft models.
Main Results:
- DHX9 expression is elevated in lung cancer.
- siDHX9 reduced proliferation and increased apoptosis, DNA damage, and R-loops.
- OE-DHX9 showed opposite effects.
- Phosphorylation mimic (OE-PKA) increased R-loops and DNA damage, while non-phosphorylatable mutant (DHX9-S279A) decreased them.
- In vivo studies confirmed DHX9's role in tumor suppression via DNA damage and R-loop induction.
Conclusions:
- Phosphorylated DHX9 enhances DNA damage by impeding R-loop resolution.
- This process ultimately inhibits lung adenocarcinoma cell proliferation.
- DHX9 phosphorylation represents a potential therapeutic target for lung cancer.
More Related Videos
Related Concept Videos
DNA Damage can Stall the Cell Cycle
DNA Damage Can Stall the Cell Cycle
Restarting Stalled Replication Forks
Abnormal Proliferation

