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Tanshinone IIA targets RNF123 to inhibit non‑small cell lung cancer cell proliferation, migration and invasion via KAT2B‑mediated H3K18ac modification

  • Authors:
    • Yongjie He
    • Yingxin Zhang
    • Jiangsheng Zhang
    • Kaican Cai
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
    Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 69
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    Published online on: December 4, 2025
       https://doi.org/10.3892/ol.2025.15422
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Abstract

Tanshinone IIA (TSIIA) exerts antitumor effects. The present study aimed to explore the pharmacological effect of TSIIA on lung cancer development and assess the potential underlying mechanism of action. Cell viability and proliferation were assessed using Cell Counting Kit‑8 and 5‑ethynyl‑20‑deoxyuridine assays, respectively. Transwell assays were performed to determine cell migration and invasion. Histone H3 lysine 18 acetylation (H3K18ac) and histone H4 lysine 8 acetylation (H4K8ac) enrichment in the RING finger protein 123 (RNF123) promoter and the interaction between lysine acetyltransferase 2B (KAT2B) and the RNF123 promoter were analyzed by chromatin immunoprecipitation assays. The results indicated that RNF123 was weakly expressed in lung cancer cells, and its upregulation decreased lung cancer cell viability, proliferation, migration, invasion and epithelial‑mesenchymal transition. Sodium TSIIA sulfate (STS) treatment inhibited the non‑small cell lung cancer (NSCLC) cell malignant phenotypes, which were reversed by the knockdown of RNF123. Mechanistically, TSIIA promoted KAT2B‑mediated H3K18ac modification at the promoter region of the RNF123 gene, leading to upregulated RNF123 expression in NSCLC cells. Additionally, KAT2B knockdown prevented the STS‑induced inhibition of NSCLC cell malignant phenotypes. Furthermore, RNF123 upregulation restored the effect of KAT2B knockdown on STS‑treated NSCLC phenotypes. In conclusion, TSIIA inhibited the NSCLC cell malignant phenotypes via the epigenetic modification of RNF123.
Introduction
View Figures

Figure 1

RNF123 is a critical mediator of
non-small cell lung cancer cell proliferation, migration and
invasion. (A) RNF123 expression in LUAD and LUSC was predicted
using the starBase database. The mRNA and protein expression levels
of RNF123 in lung cancer cells (A549, H1975, H1299, H460 and PC-9
cells) and the normal human bronchial epithelial cell line (BEAS-2B
cells) were detected by (B) RT-qPCR and (C) western blotting,
respectively. A549 and H1975 cells were transfected with
oe-RNF123/sh-RNF123 or oe-NC/sh-NC. The mRNA and protein expression
levels of RNF123 in cells were detected by (D) RT-qPCR and (E)
western blotting, respectively. (F) Cell viability was examined
using the Cell Counting Kit-8 assay. (G) The EdU assay was
performed to determine cell proliferation. Cell (H) migration and
(I) invasion were assessed using the Transwell assay in cells with
RNF123 knockdown (sh-RNF123) or overexpression (oe-RNF123). Results
are expressed as percentages relative to the control group (set as
100%). (J) E-cadherin and Vimentin protein expression levels in
cells were measured by western blotting. Data are expressed as mean
± SD (n=3). *P<0.05, **P<0.01, ***P<0.001,
****P<0.0001. RNF123, RING finger protein 123; LUAD, lung
adenocarcinoma; LUSC, lung squamous cell carcinoma; RT-qPCR,
reverse transcription-quantitative PCR; oe, overexpression; sh,
short hairpin RNA; NC, negative control; EdU,
5-ethynyl-20-deoxyuridine.

Figure 2

RNF123 knockdown reverses the
inhibitory effects of STS on non-small cell lung cancer cells. A549
and H1975 cells were treated with 5, 10, 20, 40 and 80 µM STS for
24 h. (A) CCK-8 assay was employed to detect cell viability. (B)
RT-qPCR was conducted to examined RNF123 mRNA expression level in
cells. A549 and H1975 cells were treated with 40 µM STS for 24 h
combined with sh-NC or sh-RNF123 transfection. The mRNA and protein
expression levels of RNF123 in cells were detected by (C) RT-qPCR
and (D) western blotting, respectively. (E) Cell viability was
measured by CCK-8 assay. (F) EdU assay was performed to determine
cell proliferation. Cell (G) migration and (H) invasion were
detected by Transwell assay. Results are expressed as percentages
relative to the control group (set as 100%). (I) Western blotting
was performed to examine E-cadherin and Vimentin protein expression
levels in cells. Data are expressed as mean ± SD (n=3). *P<0.05,
**P<0.01, ***P<0.001. RNF123, RING finger protein 123; STS,
sodium tanshinone IIA sulfate; CCK-8, Cell Counting Kit-8; RT-qPCR,
reverse transcription-quantitative PCR; sh, short hairpin RNA; NC,
negative control; EdU, 5-ethynyl-20-deoxyuridine.

Figure 3

STS promotes H3K18ac modification of
chromatin at the RNF123 locus in non-small cell lung cancer cells.
(A) H3K18ac, H4K8ac and H3K27ac levels in A549, H1975 and BEAS-2B
cells were assessed using western blotting. (B) The enrichment of
H3K18ac and H4K8ac in the RNF123 promoter was analyzed by ChIP
assay. A549 and H1975 cells were treated with 40 µM STS for 24 h.
(C) H3K18ac and H4K8ac protein expression levels in cells were
examined using western blotting and (D) semi-quantified. Histone
acetylation signals were normalized to total histone H3 or H4
levels, respectively. (E) H3K18ac and H4K8ac enrichment in the
RNF123 promoter was analyzed by ChIP assay. Data are expressed as
mean ± SD (n=3). *P<0.05, **P<0.01, ***P<0.001. STS,
sodium tanshinone IIA sulfate; RNF123, RING finger protein 123;
H3K18ac, histone H3 lysine 18 acetylation; H4K8ac, histone H4
lysine 8 acetylation; H3K127ac, histone H3 lysine 27 acetylation;
ChIP, chromatin immunoprecipitation.

Figure 4

STS promotes the H3K18ac modification
and expression of RNF123 by upregulating the expression of KAT2B.
(A) KAT2B expression in LUAD and LUSC was predicted using the
starBase database. The mRNA and protein expression levels of KAT2B
in A549, H1975 and BEAS-2B cells were detected by (B) RT-qPCR and
(C) western blotting, respectively. The mRNA and protein expression
levels of KAT2B in A549 and H1975 cells after STS treatment were
detected by (D) RT-qPCR and (E) western blotting, respectively. (F)
The interaction between KAT2B and RNF123 promoter was analyzed by
ChIP assay. A549 and H1975 cells were transfected with oe-NC or
oe-KAT2B. The mRNA and protein expression levels of KAT2B in cells
were detected by (G) RT-qPCR and (H) western blotting,
respectively. (I) H3K18ac enrichment in the RNF123 promoter was
analyzed by ChIP assay. The mRNA and protein levels of RNF123 in
cells were detected by (J) RT-qPCR and (K) western blotting,
respectively. Data are expressed as mean ± SD (n=3). **P<0.01,
***P<0.001, ****P<0.0001. STS, sodium tanshinone IIA sulfate;
RNF123, RING finger protein 123; H3K18ac, histone H3 lysine 18
acetylation; KAT2B, lysine acetyltransferase 2B; LUAD, lung
adenocarcinoma; LUSC, lung squamous cell carcinoma; RT-qPCR,
reverse transcription-quantitative PCR; ChIP, chromatin
immunoprecipitation; oe, overexpression; NC, negative control.

Figure 5

KAT2B knockdown reverses the
inhibitory effects of STS on the malignant phenotypes of non-small
cell lung cancer cells. KAT2B knockdown was induced in STS-treated
A549 and H1975 cells. The mRNA and protein expression levels of
KAT2B in A549 and H1975 cells after sh-NC or sh-KAT2B transfection
were detected by (A) RT-qPCR and (B) western blotting,
respectively. A549 and H1975 cells were treated with 40 µM STS for
24 h combined with sh-NC or sh-KAT2B transfection. The mRNA
expression levels of (C) KAT2B and (D) RNF123 in cells were
detected by RT-qPCR. (E) Cell viability was measured by Cell
Counting Kit-8 assay. (F) The protein expression levels of RNF123
and KAT2B in cells were detected by western blotting. (G) EdU assay
was performed to determine cell proliferation. Cell (H) migration
and (I) invasion were detected by Transwell assay. Results are
expressed as percentages relative to the control group (set as
100%). (J) E-cadherin and Vimentin protein levels in cells were
examined by western blotting. Data are expressed as mean ± SD
(n=3). *P<0.05, **P<0.01, ***P<0.001. KAT2B, lysine
acetyltransferase 2B; STS, sodium tanshinone IIA sulfate; sh, short
hairpin RNA; RT-qPCR, reverse transcription-quantitative PCR; NC,
negative control; RNF123, RING finger protein 123; EdU,
5-ethynyl-20-deoxyuridine.

Figure 6

RNF123 overexpression reverses the
effects of KAT2B knockdown on the malignant phenotypes of non-small
cell lung cancer cells treated with STS. Both RNF123 overexpression
and KAT2B knockdown were induced in STS-treated A549 and H1975
cells. The mRNA and protein expression levels of RNF123 in cells
were detected by (A) RT-qPCR and (B) western blotting,
respectively. (C) Cell viability was examined using Cell Counting
Kit-8 assay. (D) EdU assay was performed to determine cell
proliferation. Cell (E) migration and (F) invasion were assessed
using Transwell assay. Results are expressed as percentages
relative to the control group (set as 100%). (G) E-cadherin and
Vimentin protein levels in cells were measured by western blotting.
Data were expressed as mean ± SD (n=3). *P<0.05, **P<0.01,
***P< 0.001. STS, sodium tanshinone IIA sulfate; RNF123, RING
finger protein 123; KAT2B, lysine acetyltransferase 2B; RT-qPCR,
reverse transcription-quantitative PCR; NC, negative control; sh,
short hairpin RNA; oe, overexpression; EdU,
5-ethynyl-20-deoxyuridine.
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Spandidos Publications style
He Y, Zhang Y, Zhang J and Cai K: Tanshinone IIA targets RNF123 to inhibit non‑small cell lung cancer cell proliferation, migration and invasion via KAT2B‑mediated H3K18ac modification. Oncol Lett 31: 69, 2026.
APA
He, Y., Zhang, Y., Zhang, J., & Cai, K. (2026). Tanshinone IIA targets RNF123 to inhibit non‑small cell lung cancer cell proliferation, migration and invasion via KAT2B‑mediated H3K18ac modification. Oncology Letters, 31, 69. https://doi.org/10.3892/ol.2025.15422
MLA
He, Y., Zhang, Y., Zhang, J., Cai, K."Tanshinone IIA targets RNF123 to inhibit non‑small cell lung cancer cell proliferation, migration and invasion via KAT2B‑mediated H3K18ac modification". Oncology Letters 31.2 (2026): 69.
Chicago
He, Y., Zhang, Y., Zhang, J., Cai, K."Tanshinone IIA targets RNF123 to inhibit non‑small cell lung cancer cell proliferation, migration and invasion via KAT2B‑mediated H3K18ac modification". Oncology Letters 31, no. 2 (2026): 69. https://doi.org/10.3892/ol.2025.15422
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Spandidos Publications style
He Y, Zhang Y, Zhang J and Cai K: Tanshinone IIA targets RNF123 to inhibit non‑small cell lung cancer cell proliferation, migration and invasion via KAT2B‑mediated H3K18ac modification. Oncol Lett 31: 69, 2026.
APA
He, Y., Zhang, Y., Zhang, J., & Cai, K. (2026). Tanshinone IIA targets RNF123 to inhibit non‑small cell lung cancer cell proliferation, migration and invasion via KAT2B‑mediated H3K18ac modification. Oncology Letters, 31, 69. https://doi.org/10.3892/ol.2025.15422
MLA
He, Y., Zhang, Y., Zhang, J., Cai, K."Tanshinone IIA targets RNF123 to inhibit non‑small cell lung cancer cell proliferation, migration and invasion via KAT2B‑mediated H3K18ac modification". Oncology Letters 31.2 (2026): 69.
Chicago
He, Y., Zhang, Y., Zhang, J., Cai, K."Tanshinone IIA targets RNF123 to inhibit non‑small cell lung cancer cell proliferation, migration and invasion via KAT2B‑mediated H3K18ac modification". Oncology Letters 31, no. 2 (2026): 69. https://doi.org/10.3892/ol.2025.15422
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