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Emerging role of long non‑coding RNAs in the Rho/ROCK signaling pathway in tumor metastasis (Review)

  • Authors:
    • Hui Nie
    • Xuejie Yang
    • Qingning Chen
    • Xiaoyun He
    • Yingying Han
    • Qiuyan He
    • Chunlin Ou
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
    Copyright: © Nie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 197
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    Published online on: September 12, 2025
       https://doi.org/10.3892/ijmm.2025.5638
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Abstract

Metastasis is a critical feature of malignant tumors and a major cause of treatment failure and poor prognosis. This complex process primarily involves the rearrangement of the cytoskeleton. Among several cytoskeleton‑associated signaling pathways, the ras homolog family (Rho) and Rho‑associated coiled‑coil containing protein kinase (ROCK) signaling pathway serves a key role in cytoskeleton regulation as it controls intracellular actin dynamics and cytoskeletal remodeling to mediate cell movement. Long non‑coding RNAs (lncRNAs), known to serve important roles in tumorigenesis and metastasis, have been shown to regulate the Rho/ROCK pathway. lncRNAs modulate the Rho/ROCK pathway by sponging microRNAs or directly binding to proteins, thereby mediating tumor metastasis. Additionally, lncRNAs can be encapsulated in exosomes and transferred from donor cells to recipient cells, where they regulate components of the Rho/ROCK signaling pathway and further promote the metastatic potential. Based on their functional significance, Rho/ROCK signaling pathway‑associated lncRNAs may serve as novel tumor biomarkers and therapeutic targets. The present review summarizes the role and mechanism of Rho/ROCK signaling pathway‑associated lncRNAs in tumor metastasis, which may offer novel avenues for the diagnosis and treatment of metastatic cancer.
View Figures

Figure 1

Members of the Rho family. The main
members of the Rho family include the Rnd, Rac, Rho, Cdc42 and
RhoBTB subfamilies. The members of the Rho subfamily include RhoA,
RhoB and RhoC. The members of the Rho subfamily regulate the
cytoskeleton by modulating the ROCK/MLCP and ROCK/LIMK pathways.
Cdc42, cell division cycle 42; LIMK, LIM domain kinase; MLCP,
myosin light chain phosphatase; Rac, Ras-related C3 botulinum toxin
substrate; Rho, Rho family GTPases; RhoBTB, Rho-related BTB
domain-containing; Rnd, Rho family GTPase; ROCK, Rho-associated
coiled-coil containing protein kinase.

Figure 2

lncRNAs promote tumor invasion and
metastasis by regulating the Rho/ROCK signaling pathway. (A) lncRNA
lnc00892 inhibits metastasis of bladder cancer by binding to c-Jun,
a protein in the activator protein-1 transcription complex, which
reduces transcription of the nucleolin gene and the stability of
RhoA/RhoC mRNA in the Rho/ROCK signaling pathway. (B) lncRNA NORAD
inhibits the RhoA/ROCK signaling pathway by interfering with CXCR4,
which inhibits the proliferation, invasion and migration of
non-small cell lung cancer cells. (C) lncRNA ABHD11-AS1 binds to
RhoC and promotes the proliferation, invasion and migration of
ovarian cancer cells. (D) lncRNA MER52A promotes the invasion and
metastasis of hepatocellular carcinoma cells by stabilizing
P120-catenin and activating the downstream target molecules Rac1
and Cdc42. Cdc42, cell division cycle 42; CXCR, CXC chemokine
receptor; LIMK, LIM domain kinase; lncRNA/lnc, long non-coding RNA;
NCL, nucleolin; Rac, Ras-related C3 botulinum toxin substrate; Rho,
Rho family GTPases; ROCK, Rho-associated coiled-coil containing
protein kinase.

Figure 3

Effect of long non-coding RNAs on
tumor metastasis in vivo. (A) A mouse xenograft model was
established. HCC cells with stable expression of shLINC00161 were
injected into the tail vein, and tumor growth and metastasis in
mice were observed (154). The
study aimed to demonstrate the effect of lncRNAs on HCC metastasis
in an in vivo model. (B) KFTX OC cells with high expression
of UCA1 were intraperitoneally injected into mice, then
OVV-VGFΔ/O1LΔ was intraperitoneally injected into mice, and the
tumor growth was observed (210). The study aimed to demonstrate
the effect of lncRNAs on OC metastasis in an in vivo model.
Cdc42, cell division cycle 42; HCC, hepatocellular carcinoma;
lncRNA, long non-coding RNA; OC, ovarian cancer; OVV-VGFΔ/O1LΔ,
oncolytic vaccinia virus-VGF deleted/O1L deletion; PTX, paclitaxel;
sh, short hairpin RNA; UCA1, urothelial carcinoma-associated 1.
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Copy and paste a formatted citation
Spandidos Publications style
Nie H, Yang X, Chen Q, He X, Han Y, He Q and Ou C: Emerging role of long non‑coding RNAs in the Rho/ROCK signaling pathway in tumor metastasis (Review). Int J Mol Med 56: 197, 2025.
APA
Nie, H., Yang, X., Chen, Q., He, X., Han, Y., He, Q., & Ou, C. (2025). Emerging role of long non‑coding RNAs in the Rho/ROCK signaling pathway in tumor metastasis (Review). International Journal of Molecular Medicine, 56, 197. https://doi.org/10.3892/ijmm.2025.5638
MLA
Nie, H., Yang, X., Chen, Q., He, X., Han, Y., He, Q., Ou, C."Emerging role of long non‑coding RNAs in the Rho/ROCK signaling pathway in tumor metastasis (Review)". International Journal of Molecular Medicine 56.6 (2025): 197.
Chicago
Nie, H., Yang, X., Chen, Q., He, X., Han, Y., He, Q., Ou, C."Emerging role of long non‑coding RNAs in the Rho/ROCK signaling pathway in tumor metastasis (Review)". International Journal of Molecular Medicine 56, no. 6 (2025): 197. https://doi.org/10.3892/ijmm.2025.5638
Copy and paste a formatted citation
x
Spandidos Publications style
Nie H, Yang X, Chen Q, He X, Han Y, He Q and Ou C: Emerging role of long non‑coding RNAs in the Rho/ROCK signaling pathway in tumor metastasis (Review). Int J Mol Med 56: 197, 2025.
APA
Nie, H., Yang, X., Chen, Q., He, X., Han, Y., He, Q., & Ou, C. (2025). Emerging role of long non‑coding RNAs in the Rho/ROCK signaling pathway in tumor metastasis (Review). International Journal of Molecular Medicine, 56, 197. https://doi.org/10.3892/ijmm.2025.5638
MLA
Nie, H., Yang, X., Chen, Q., He, X., Han, Y., He, Q., Ou, C."Emerging role of long non‑coding RNAs in the Rho/ROCK signaling pathway in tumor metastasis (Review)". International Journal of Molecular Medicine 56.6 (2025): 197.
Chicago
Nie, H., Yang, X., Chen, Q., He, X., Han, Y., He, Q., Ou, C."Emerging role of long non‑coding RNAs in the Rho/ROCK signaling pathway in tumor metastasis (Review)". International Journal of Molecular Medicine 56, no. 6 (2025): 197. https://doi.org/10.3892/ijmm.2025.5638
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