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LRRC59 inhibits perk pathway‑induced apoptosis and promotes cell proliferation, migration and invasion in colorectal cancer cells

  • Authors:
    • Xingdong Hou
    • Yuting Wang
    • Yuzhuo Chen
    • Peiyan Zhong
    • Guangzhi Wang
    • Baicheng Li
    • Bowei Lu
    • Hanyu Jiang
    • Shili Ning
  • View Affiliations / Copyright

    Affiliations: Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China, Department of Thoracic Surgery, Binzhou People's Hospital, Binzhou, Shandong 256610, P.R. China, Department of Clinical Nutrition, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China, Department of Thyroid Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China, Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116000, P.R. China
    Copyright: © Hou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 5
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    Published online on: October 23, 2025
       https://doi.org/10.3892/or.2025.9010
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Abstract

Leucine‑rich repeat‑containing protein 59 (LRRC59), a 244‑amino‑acid endoplasmic reticulum membrane protein, is implicated in the tumorigenesis of multiple malignancies. However, its functional significance in colorectal cancer (CRC) remains poorly understood. In the present study, LRRC59 expression in CRC tissues was evaluated using immunohistochemistry and western blotting. Colony formation, Cell Counting Kit‑8, wound healing and Transwell assays, in in vivo xenograft models, were used to evaluate the effect of LRRC59 on CRC progression. Apoptosis was analyzed using flow cytometry and western blotting. The interaction between LRRC59 and the protein kinase RNA‑like endoplasmic reticulum kinase (PERK) pathway was verified using the starBase database and western blotting. It was found that LRRC59 expression was significantly higher in CRC tissues than in normal tissues. LRRC59 knockdown in HCT116 and LoVo cells inhibited proliferation, migration and invasion and promoted apoptosis, and the PERK pathway was significantly activated. In vivo subcutaneous tumorigenesis assays corroborated these in vitro findings. Treatment with a PERK pathway‑specific inhibitor reduced the apoptosis of HCT116 and LoVo cells with LRRC59 knockdown. These findings suggest that LRRC59 is not only significantly upregulated in CRC but also mechanistically drives tumor progression by coordinating pro‑oncogenic processes, including enhanced proliferation, migration and invasion. Importantly, mechanistic evidence was provided that LRRC59 inhibits apoptosis by suppressing the PERK signaling axis, identifying this molecule a target in the development of CRC therapeutic strategies.
View Figures

Figure 1

LRRC59 upregulation in CRC tissues.
(A-C) mRNA expression of LRRC59 in CRC tissues was analyzed using
(A) the TIMER2.0, (B) GEPIA and (C) The Cancer Genome Atlas
databases. (D) Immunohistochemistry and (F) H-score of LRRC59 in
normal versus CRC tissues. (E and G) Western blot analysis of
LRRC59 protein in CRC and normal tissues. Scale bars, 50 and 200
µm. *P<0.05, **P<0.01 and ***P<0.001. CRC, colorectal
cancer; COAD, colon adenocarcinoma; READ, rectum
adenocarcinoma.

Figure 2

LRRC59 enhances CRC cell
proliferation. (A and B) Efficiency of si-LRRC59 transfection in
HCT116 and LoVo cells confirmed by reverse
transcription-quantitative PCR. (C, F and G) Western blot analysis
of LRRC59 expression in si-NC and si-LRRC59 transfected cells. (D
and E) Cell proliferation rates were evaluated using the Cell
Counting Kit-8 assay on days 1, 2, and 3 following transfections.
(H-J) Colony formation assays evaluating the tumorigenic potential
of CRC cells. *P<0.05, **P<0.01 and ***P<0.001. CRC,
colorectal cancer; si-, small interfering; NC, negative
control.

Figure 3

LRRC59 facilitates migration and
invasion in colorectal cancer cells. (A, B and E-H) Migratory
potential evaluated using Transwell and wound healing assays. (C
and D) Invasive capacity was assessed through Transwell assays with
Matrigel. Scale bars, 200 and 500 µm. **P<0.01 and
***P<0.001. si-, small interfering; NC, negative control.

Figure 4

LRRC59 regulates the PERK-mediated
ERS signaling pathway. (A) According to the starBase database,
LRRC59 is associated with ERS pathway key genes GRP78, ATF4, and
CHOP in colorectal cancer. (B-D) Western blot analysis of PERK
pathway-related proteins (GRP78, p-PERK, PERK, ATF4, p-EIF2α, EIF2α
and CHOP). *P<0.05, **P<0.01 and ***P<0.001. ER,
endoplasmic reticulum; PERK, protein kinase RNA-like ER kinase;
ERS, ER stress; p-, phosphorylated; si-, small interfering; NC,
negative control; COAD, colon adenocarcinoma.

Figure 5

LRRC59 suppresses apoptosis in
colorectal cancer cells. (A-D) Flow cytometry of apoptosis in
LRRC59 knockdown HCT116 and LoVo cells. (E-G) Western blot analysis
of apoptosis-related proteins (Bcl-2, Bax, Caspase3 and
active-caspase3) in transfected cells. *P<0.05, **P<0.01 and
***P<0.001. si-, small interfering; NC, negative control.

Figure 6

LRRC59 inhibits apoptosis in
colorectal cancer cells by suppressing the PERK-mediated ERS
signaling pathway. LRRC59 knockdown HCT116 and LoVo cells were
treated with GSK (1 µM). (A-C) Expression of PERK-mediated ERS
signaling proteins and apoptosis-related proteins was detected by
western blot analysis. (D-G) Flow cytometric analysis of apoptosis.
*P<0.05, **P<0.01 and ***P<0.001. ER, endoplasmic
reticulum; PERK, protein kinase RNA-like ER kinase; ERS, ER stress;
p-, phosphorylated; si-, small interfering; NC, negative
control.

Figure 7

LRRC59 enhances colorectal cancer
progression in mouse models. (A and B) Western blot analysis of
LRRC59 expression in sh-NC and sh-LRRC59 LoVo cells. (C and D)
Images of mice and tumors from sh-NC and sh-LRRC59 groups. (E and
G) Tumor volumes measured every 3 days; final tumor weights
recorded after 34 days. (F) Body weight trends remained unchanged.
(H and I) Immunohistochemistry analysis of PERK pathway activation.
Scale bar, 200 µm. *P<0.05, **P<0.01 and ***P<0.001. ER,
endoplasmic reticulum; PERK, protein kinase RNA-like ER kinase;
sh-, short hairpin; NC, negative control; p-, phosphorylated; ns,
non-significant.
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Copy and paste a formatted citation
Spandidos Publications style
Hou X, Wang Y, Chen Y, Zhong P, Wang G, Li B, Lu B, Jiang H and Ning S: LRRC59 inhibits perk pathway‑induced apoptosis and promotes cell proliferation, migration and invasion in colorectal cancer cells. Oncol Rep 55: 5, 2026.
APA
Hou, X., Wang, Y., Chen, Y., Zhong, P., Wang, G., Li, B. ... Ning, S. (2026). LRRC59 inhibits perk pathway‑induced apoptosis and promotes cell proliferation, migration and invasion in colorectal cancer cells. Oncology Reports, 55, 5. https://doi.org/10.3892/or.2025.9010
MLA
Hou, X., Wang, Y., Chen, Y., Zhong, P., Wang, G., Li, B., Lu, B., Jiang, H., Ning, S."LRRC59 inhibits perk pathway‑induced apoptosis and promotes cell proliferation, migration and invasion in colorectal cancer cells". Oncology Reports 55.1 (2026): 5.
Chicago
Hou, X., Wang, Y., Chen, Y., Zhong, P., Wang, G., Li, B., Lu, B., Jiang, H., Ning, S."LRRC59 inhibits perk pathway‑induced apoptosis and promotes cell proliferation, migration and invasion in colorectal cancer cells". Oncology Reports 55, no. 1 (2026): 5. https://doi.org/10.3892/or.2025.9010
Copy and paste a formatted citation
x
Spandidos Publications style
Hou X, Wang Y, Chen Y, Zhong P, Wang G, Li B, Lu B, Jiang H and Ning S: LRRC59 inhibits perk pathway‑induced apoptosis and promotes cell proliferation, migration and invasion in colorectal cancer cells. Oncol Rep 55: 5, 2026.
APA
Hou, X., Wang, Y., Chen, Y., Zhong, P., Wang, G., Li, B. ... Ning, S. (2026). LRRC59 inhibits perk pathway‑induced apoptosis and promotes cell proliferation, migration and invasion in colorectal cancer cells. Oncology Reports, 55, 5. https://doi.org/10.3892/or.2025.9010
MLA
Hou, X., Wang, Y., Chen, Y., Zhong, P., Wang, G., Li, B., Lu, B., Jiang, H., Ning, S."LRRC59 inhibits perk pathway‑induced apoptosis and promotes cell proliferation, migration and invasion in colorectal cancer cells". Oncology Reports 55.1 (2026): 5.
Chicago
Hou, X., Wang, Y., Chen, Y., Zhong, P., Wang, G., Li, B., Lu, B., Jiang, H., Ning, S."LRRC59 inhibits perk pathway‑induced apoptosis and promotes cell proliferation, migration and invasion in colorectal cancer cells". Oncology Reports 55, no. 1 (2026): 5. https://doi.org/10.3892/or.2025.9010
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