SF3B3 overexpression promotes proliferation of gastric cancer cells and correlates with poor patient prognosis

doi:10.12122/j.issn.1673-4254.2025.10.20

Abstract

Abstract:

Objective To investigate the role of SF3B3 in gastric cancer (GC) progression and prognosis and its possible mechanisms. Methods SF3B3 expression levels in pan-cancer and GC were analyzed using TIMER2.0, GEPIA, and UALCAN databases and validated using immunohistochemistry in GC tissues. Survival curves of GC patients were established using Kaplan-Meier Plotter and the data of a patient cohort our hospital. The independent risk factors for 5-year postoperative survival were identified using Cox regression, and their predictive values were evaluated using ROC analysis. SF3B3-associated biological processes were predicted by bioinformatics enrichment analyses. In GC HGC-27 cells, the effects of lentivirus-mediated SF3B3 knockdown and overexpression on cell proliferation and migration were investigated, and the changes in the key glycolytic proteins and extracellular acidification rate (ECAR) were detected. The influence of SF3B3 expression level on tumorigenesis and glycolytic protein expression in vivo were evaluated in a nude mouse xenograft model. Results High expression of SF3B3 in GC was associated with poor patient prognosis (P<0.05). The factors affecting 5-year survival outcomes following gastric oncological resection included high SF3B3 expression, a CEA level ≥5μg/L, a CA19-9 level ≥37 kU/L, tumor stage T3-4, and lymph node metastasis stage N2-3 (P<0.05). Bioinformatics analysis showed significant enrichment of SF3B3 in glycolysis. In HGC-27 cells, SF3B3 knockdown significantly inhibited while SF3B3 overexpression enhanced cell proliferation, migration, and invasion. SF3B3 knockdown obviously decreased the expressions of HK2, PKM2 and LDHA proteins and ECAR in HGC-27 cells, whereas SF3B3 overexpression produced the opposite effect. In nude mouse xenograft models, SF3B3 knockdown significantly reduced tumor mass and downregulated expression of HK2, PKM2 and LDHA proteins, and SF3B3 overexpression induced the opposite changes. Conclusion SF3B3 overexpression is associated with poor prognosis of GC patients and promotes GC cell proliferation, migration and invasion possibly by enhancing glycolysis.

Key words: gastric cancer, SF3B3, poor prognosis, glycolysis

Hui LU, Bowen SONG, Jinran SHI, Shunyin WANG, Xiaohua CHEN, Jingjing YANG, Sitang GE, Lugen ZUO. SF3B3 overexpression promotes proliferation of gastric cancer cells and correlates with poor patient prognosis[J]. Journal of Southern Medical University, 2025, 45(10): 2240-2249.

Figures/Tables 6

Fig.1 Overexpression of SF3B3 in stomach adenocarcinoma. A: Differential expression profiles of SF3B3 in diverse cancerous lesions. B, C: Analysis of SF3B3 expression between gastric cancer and adjacent benign tissues. D, E: Immunohistochemistry for SF3B3 in paired gastric carcinoma and adjacent normal tissues. *P<0.05, **P<0.01, ***P<0.001.

Tab.1 SF3B3 expression patterns in relation to clinicopathological features of gastric cancer patients

Factor	n	SF3B3 expression (n, %)		χ²	P
Factor	n	Low (n=53)	High (n=54)	χ²	P
Gender
Male	45	26 (57.78%)	19 (42.22%)	2.112	0.146
Female	62	27 (43.55%)	35 (56.45%)
Age (year)
<60	36	18 (50.00%)	18 (50.00%)	0.005	0.945
≥60	71	35 (49.30%)	36 (50.70%)
CEA (μg/L)
<5	51	36 (70.59%)	15 (29.41%)	17.282	<0.001
≥5	56	17 (30.36%)	39 (69.64%)
CA19-9 (kU/L)
<37	53	36 (67.92%)	17 (32.08%)	14.211	<0.001
≥37	54	17 (31.48%)	37 (68.52%)
Tumor size (cm)
<5	49	28 (57.14%)	21 (42.86%)	2.094	0.148
≥5	58	25 (43.10%)	33 (56.90%)
Histological type
Adenocarcinoma	84	44 (52.38%)	40 (47.62%)	1.268	0.260
Other	23	9 (39.13%)	14 (60.87%)
Pathological grading
G1-G2	53	27 (50.94%)	26 (49.06%)	0.084	0.772
G3-G4	54	26 (48.15%)	28 (51.85%)
T stage
T1-T2	48	31 (64.58%)	17 (35.42%)	7.888	0.005
T3-T4	59	22 (37.29%)	37 (62.71%)
N stage
N0-N1	63	40 (63.49%)	23 (36.51%)	11.943	<0.001
N2-N3	44	13 (29.55%)	31 (70.45%)

Fig.3 SF3B3 expression level is an independent risk factor for prognosis of gastric cancer patients.

Fig.4 Prognostic value of SF3B3 expression for 5-year survival outcomes of gastric cancer patients following surgical intervention.

Fig.6 Elevated SF3B3 levels enhance proliferative, migration, and invasive abilities of HGC-27 cells. A: Impact of SF3B3 knockdown on proliferation of HGC-27 cells. B: Impact of SF3B3 overexpression on proliferation of HGC-27 cells. C-F: Assessment of migration and invasion of HGC-27 cells. NC: Negative control; sh-NC: Short hairpin RNA negative control; LV-NC: Lentivirus negative control. *P<0.05 vs NC.

Fig.8 Role of SF3B3 in augmenting tumorigenesis in nude mice and its impact on glycolytic activity in vivo. A: Comparison of xenograft growth among the groups. B, C: Measurement of tumor weight in nude mice. D, E: Quantification of tumor volume in nude mice. F-H: Assessment of HK2, PKM2, and LDHA protein expression using Western blotting in tumor xenografts. *P<0.05 vs sh-NC or LV-NC group.

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