Open Access

RFC3 drives the proliferation, migration, invasion and angiogenesis of colorectal cancer cells by binding KIF14

  • Authors:
    • Rong Yu
    • Xinxin Wu
    • Fang Qian
    • Qian Yang
  • View Affiliations

  • Published online on: March 22, 2024
  • Article Number: 222
  • Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Colorectal cancer (CRC) is a deadly and aggressive type of cancer that has a high fatality rate. The expression levels of replication factor C subunit 3 (RFC3) and kinesin family member 14 (KIF14) have been reported to be increased in CRC. The current study aimed to explore the effects of RFC3 on the malignant behaviors of CRC cells and its possible underlying mechanism involving KIF14. RFC3 and KIF14 expression levels in CRC tissues were analyzed using TNMplot database and Gene Expression Profiling Interactive Analysis database bioinformatics tools. RFC3 and KIF14 levels in CRC cells were examined using reverse transcription‑quantitative PCR and western blotting. Cell Counting Kit‑8 and 5‑ethynyl‑2'‑deoxyuridine assays were performed to assess cell proliferation. Cell apoptosis was determined using flow cytometric analysis. Wound healing and Transwell assays were adopted for the evaluation of cell migration and invasion. Tube formation assay in human umbilical vein endothelial cells was used to measure angiogenesis. Western blotting analysis was performed to determine the expression of apoptosis‑, migration‑ and angiogenesis‑associated proteins. Additionally, bioinformatics tools predicted the co‑expression and interaction of RFC3 and KIF14, which was verified by a co‑immunoprecipitation assay. RFC3 displayed elevated expression in CRC tissues and cells, and depletion of RFC3 halted the proliferation, migration, invasion and angiogenesis, while increasing the apoptosis of CRC cells; this was accompanied by changes in the expression levels of related proteins. In addition, RFC3 bound to KIF14 and interference with RFC3 reduced KIF14 expression. Moreover, KIF14 upregulation reversed the effects of RFC3 depletion on the aggressive cellular behaviors in CRC. In conclusion, RFC3 might interact with KIF14 to function as a contributor to the malignant development of CRC.


Colorectal cancer (CRC) is an aggressive tumor that originates in the inner wall of the large intestine. Overall, according to recent statistics, it has been estimated that ~153,000 cases of CRC will be reported in 2023, of which >1/3 may die of this disease, thus accounting for ~10% of all cancer-associated mortalities (1,2). Despite the favorable prognosis of patients with early-stage CRC after the application of comprehensive and evidence-based therapies, such as a combination of surgery, chemotherapy, targeted therapy and/or radiation (3), most patients with CRC at advanced stages will develop recurrence and distant metastasis in the course of the disease, resulting in a poor outcome (4). Growing evidence has indicated that epigenetic alterations participate in the process of CRC (5,6). Therefore, insight into the mechanism underlying the malignant development of CRC and any effective biomarkers may result in the identification of novel therapeutic regimes for CRC.

Replication factor C (RFC) is a component of the eukaryotic DNA polymerase involved in DNA replication, DNA damage repair and checkpoint control (7,8). As a subunit of the RFC family, RFC subunit 3 (RFC3), originally purified from HeLa cells, has been determined to play an essential role in the in vitro replication of Simian virus 40(9). Previous evidence has expounded that RFC3 is highly expressed in lung adenocarcinoma (10), ovarian carcinoma (11), hepatocellular carcinoma (12) and triple-negative breast cancer cells (13), and that it drives the aggressive biological phenotypes of cells, such as migration and invasion (13). All of these findings have identified RFC3 as a potential oncogene. Furthermore, RFC3 is upregulated in CRC tissues and RFC3 alteration shows worse disease-free survival of patients with CRC (14). However, the effect of RFC3 on CRC cells in vitro remains to be elucidated.

Kinesin, a cytoskeletal motor, is responsible for the intracellular transport of organelles and vesicles along microtubules (15). As reported, kinesin extensively participates in a variety of diseases (16,17). Belonging to the kinesin-3 family, the functions of kinesin family member 14 (KIF14) are also dependent on microtubules. Notably, KIF14 has been proposed as a tumor promoter in multiple human malignancies, including cervical cancer (18), gastric cancer (19) and retinoblastoma (20). Notably, Wang et al has suggested that KIF14, targeted by microRNA (miR)-200c, activates Akt to elicit pro-proliferation activities in CRC (21). The present study planned to investigate the possible interaction between RFC3 and KIF14.

The present research was designed to identify the effects of RFC3 and KIF14 on the proliferation, migration, invasion and angiogenesis of CRC. Furthermore, the possible interaction between RFC3 and KIF14 was explored to reveal the potential mechanism. This study may expose a novel therapeutic target for CRC treatment.

Materials and methods

Bioinformatics tools

The TNMplot database ( was used to analyze the expression levels of RFC3 and KIF14 in CRC (tumor) tissues and normal tissues. Gene Expression Profiling Interactive Analysis (GEPIA) database ( were also employed to evaluate the expression levels of RFC3 and KIF14 in colon adenocarcinoma (COAD) tissues and normal tissues (the original image downloaded from GEPIA database displayed in the form of log transformation). The survival analyses were performed using the KM-plot ( database. Coexpedia database ( and Biogrid database ( were used to predict the co-expression between RFC3 and KIF14.

Cell culture and treatment

CRC cell lines (SW620, HCT8 and HCT 116) and human umbilical vein endothelial cells (HUVECs) were all procured from BeNa Culture Collection (Beijing Beina Chunglian Institute of Biotechnology), while the human normal intestinal epithelial cell line (HIEC-6) was purchased from Shanghai Yaji Biological Technology Co., Ltd. HCT8 and HCT 116 cells were subjected to cultivation in RPMI-1640 medium (Wisent Biotechnology), while the SW620 cell line was maintained in DMEM (Wisent Biotechnology). The aforementioned media were both supplemented with 10% fetal bovine serum (FBS; Wisent Biotechnology) under the atmosphere of 5% CO2 at 37˚C. Opti-MEM (Invitrogen; Thermo Fisher Scientific, Inc.) supplemented with 10 ng/ml epidermal growth factor (EGF), 4% FBS, 20 mM HEPES and 10 mM GlutaMAX was prepared for the incubation of HIEC-6 cells, while endothelial cell medium (Shenzhen Aipunuo Biotechnology Co., Ltd.) containing 1% ECGS and 10% FBS was prepared for the cultivation of HUVECs. When cell confluence reached 80%, the cells were digested with 0.25% trypsin (Beyotime Institute of Biotechnology) and centrifuged at 800 x g for 5 min at room temperature. After discarding the supernatant, the cells were resuspended in PBS and adjusted to a cell density of 3x105/ml. The cell suspension (1 ml) was collected and seeded in a six-well culture plate, which was placed overnight in an incubator under the same conditions as those aforementioned.


SW620 cells (3x105 cells/well) were inoculated onto six-well plates and cultured at 37˚C with 5% CO2 until the cell confluence reached 85%. RFC3-labeled small interfering RNAs (siRNAs) (si-RFC3-1, 5'-GCATTGAAGATATTTGCCACGTGTT-3'; si-RFC3-2, 5'-GAGATAATAATGAAGGGCCTTCTCT-3') or the nonsense siRNA (siRNA-NC, 5'-GCAAAGTAGTTACGATTCATGATCT-3') provided by Vigene Biosciences (Charles River Laboratories, Inc.), and the KIF14 pcDNA3.1 overexpression plasmid (Ov-KIF14) or empty vector pcDNA3.1 plasmid (Ov-NC) synthesized by Tsingke Biological Technology, were transfected into SW620 cells using Lipofectamine 2000 (Invitrogen; Thermo Fisher Scientific, Inc.) as per the manufacturer's instructions. At 48 h after transfection, the cells were harvested to conduct the subsequent experiments.

Reverse transcription-quantitative PCR (RT-qPCR)

Following total RNA isolation from several CRC cell lines (SW620, HCT8 and HCT 116) or HIEC-6 cells using TRIzol® reagent (Invitrogen; Thermo Fisher Scientific, Inc.), cDNA was acquired with the aid of the First-strand cDNA Synthesis Kit (Thermo Fisher Scientific, Inc.) according to the manufacturer's protocol. Then, SYBR green PCR Master mix (KAPA Biosystems; Roche Diagnostics) was adopted for qPCR analysis, using cDNA as a template. The PCR reaction conditions consisted of 95˚C for 3 min, followed by 40 cycles of 95˚C for 30 sec and 60˚C for 30 sec. Relative RFC3 and KIF14 expression levels were calibrated in terms of the 2-ΔΔCq approach (22). GAPDH functioned as a normalization gene. The primer sequences were as follows: RFC3, forward 5'-GTGGACAAGTATCGGCCCTG-3' and reverse 5'-TGATGGTCCGTACACTAACAGAT-3'; KIF14, forward 5'-CCTCACCCACAGTAGCCGA-3' and reverse 5'-AAGTGCCAATCTACCTACAGGA-3'; GAPDH forward 5'-TGTGGGCATCAATGGATTTGG-3' and reverse 5'-ACACCATGTATTCCGGGTCAAT-3'.

Western blotting

RIPA lysis buffer (Beyotime Institute of Biotechnology) was added to cells in each well and placed on ice for 20 min. After centrifugation at 800 x g at 4˚C for 10 min, the supernatant was obtained to detect the total protein concentration using a bicinchoninic acid kit (Beyotime Institute of Biotechnology). Then, the equal amount of proteins (40 µg/lane) was separated by 10% SDS-PAGE and transferred to PVDF membranes. After being pre-coated with 5% BSA (Beyotime Institute of Biotechnology) for 1 h at room temperature, the membranes were successively labeled with RFC3 (cat. no. ab182143; 1/1,000; Abcam), KIF14 (cat. no. ab71155; ½,000; Abcam), B cell lymphoma 2 (BCL2; cat. no. ab182858; 1/2,000; Abcam), BCL2-associated X (Bax; cat. no. ab32503; 1/1,000; Abcam), cleaved caspase 3 (cat. no. ab32042; 1/500; Abcam), matrix metallopeptidase 2 (MMP2; cat. no. ab92536; 1/1,000; Abcam), matrix metallopeptidase 9 (MMP9; cat. no. ab76003; 1/1,000; Abcam), vascular EGF (VEGF; cat. no. sc-57496; 1/1,000; Santa Cruz Biotechnology, Inc.) and VEGF receptor 1 (VEGFR1; cat. no. ab32152; 1/1,000; Abcam) primary antibodies overnight at 4˚C, followed by incubation with goat anti-rabbit IgG (cat. no. ab97051; 1/2,000; Abcam) or goat anti-mouse IgG (cat. no. ab6789; ½,000; Abcam) for 1 h at room temperature. The blots were visualized using the enhanced chemiluminescence detection reagent (Shanghai Yeasen Biotechnology Co., Ltd.) and densitometric analysis was performed with ImageJ software (version 1.49; National Institutes of Health).

Cell Counting Kit-8 (CCK-8) assay

After transfection, SW620 cells were injected into 96-well plates (1,000 cells/well). With the help of a microplate reader (Shenzhen Reagent Technology Co., Ltd.), the OD 450 nm value was estimated, after each well was loaded with 10 µl CCK-8 solution (Beyotime Institute of Biotechnology) for 2 h of incubation.

5-Ethynyl-2'-deoxyuridine (EDU) staining

Cell proliferation was measured using an EDU staining kit (Beijing Solarbio Science & Technology Co., Ltd.). Transiently transfected SW620 cells (5,000 cells/well) were seeded into 96-well plates supplemented with 50 µM EDU for 2 h in compliance with the manufacturer's protocol. Following 30 min of immobilization with 4% paraformaldehyde at 37˚C and 10 min of permeation with 1% Triton X-100 at 37˚C, cells were stained with DAPI for 30 min at room temperature. Images were prepared for observation under a fluorescence microscope (Leica Microsystems GmbH).

Flow cytometric analysis

After the indicated treatment, SW620 cells in each group were routinely digested with 0.25% trypsin (Beyotime Institute of Biotechnology) for 10 min at room temperature, followed by washing with PBS three times and centrifugation at 2,000 x g for 3 min at 4˚C. Then, the supernatant was discarded, and the cell concentration was adjusted to 5x105 cells per sample. Cells were mixed with 5 µl Annexin V-FITC (Multisciences (Lianke) Biotech Co., Ltd.) and 5 µl propidium iodide (Multisciences (Lianke) Biotech Co., Ltd.) for 15 min at room temperature. Analysis of cell apoptosis was performed using BD FACSAria flow cytometry (BD Biosciences). FlowJo vX.0.7 software (FlowJo LLC) was used to assess the rates of apoptosis.

Wound healing assay

SW620 cells were inoculated in six-well plates (4x105 cells/well). After cells reached 90% confluence, a straight wound was gently made on the surface of the plate via the application of a 200-µl pipette tip The suspended cells were then submerged in DMEM deprived of serum. A light microscope (Leica Microsystems GmbH) was used to detect the wound area at 0 and 24 h. The extent of wound healing was calculated as follows: Migration (%)=(wound area at 0 h-wound area at 24 h)/wound area at 0 h.

Transwell assay

The upper sides of Transwell inserts (8 µm; Corning, Inc.) coated with Matrigel (BD Biosciences) at 37˚C for 1 h were loaded with SW620 cells (5x104 cells/well) in DMEM deprived of serum, whereas 500 µl DMEM containing 10% FBS was added to the undersides as a chemoattractant. After 24 h incubation at 37˚C, the remaining cells were cleared while the invaded cells were stained with crystal violet for 10 min at room temperature and images were captured under a light microscope.

Tube formation assay

Prior to the implementation of the tube formation assay, conditioned medium (CM) was harvested after the culture medium of SW620 cells in six-well plates was changed to DMEM deprived of serum. Subsequently, HUVECs (1x105) were spread onto 96-well plates precoated with Matrigel at 37˚C for 1 h in CM. Tubules were observed under an inverted light microscope and subjected to analysis with ImageJ software (version 1.49; National Institutes of Health).

Co-immunoprecipitation (Co-IP) assay

The Co-IP assay was conducted using the Co-IP kit [cat. no. abs9649-50T; Aibixin (Shanghai) Biotechnology Co., Ltd.]. Briefly, SW620 cells were lysed on ice for 30 min in radioimmunoprecipitation assay (RIPA) lysis buffer (Beyotime Institute of Biotechnology). Next, 2 µg RFC3 (cat. no. 11814-1-AP; Proteintech Group, Inc.), KIF14 (cat. no. ab71155; Abcam) or goat anti-rabbit IgG (the negative control; cat. no. ab172730; Abcam) antibodies were added to 500 µg SW620 cell lysates and incubated overnight at 4˚C. Subsequently, 50 µg protein A magnetic beads (cat. no. #sc-2003; Santa Cruz Biotechnology, Inc.) were added for capturing the complexes of RFC3 and KIF14. After the IP reaction, 50 µg protein G/A agarose beads were centrifuged at 1,000 x g for 3 min at 4˚C to the bottom of the tube. The supernatant was then carefully absorbed, and the agarose beads were washed three times with PBS. A total of 15 µl 2X SDS sample buffer was finally added for boiling at 100˚C for 5 min. The immunoprecipitants were analyzed by western blotting.

Statistical analyses

The data are presented as the mean ± standard deviation from three independent experiments adopting GraphPad Prism 8 software (GraphPad Software, Inc.; Dotmatics). One-way ANOVA followed by Tukey's test was used to analyze data. P<0.05 was considered to indicate a statistically significant difference.


RFC3 displays upregulated expression in CRC cells

RFC3 expression in CRC tissues was analyzed by using TNMplot and GEPIA databases. As shown in Fig. 1A and B, RFC3 was highly expressed in CRC tumor tissues compared with the normal tissues. To figure out the specific role of RFC3 in CRC, RFC3 expression was detected by RT-qPCR and western blotting. As shown in Fig. 1C and D, RFC3 mRNA and protein expression levels were both significantly increased in SW620, HCT8 and HCT 116 cells compared with those in the HIEC-6 cell line. Notably, SW620 cells exhibited the most prominently elevated RFC3 expression, and were thus selected for the follow-up experiments.

RFC3 depletion diminishes the proliferation and aggravates the apoptosis of CRC cells

To specify the effects of RFC3 on the aggressive process of CRC, RFC3 expression was silenced prior to the implementation of loss-of-function experiments. After transfection with si-RFC3-1/2, there was a significant decrease in both RFC3 mRNA and protein expression levels compared with the siRNA-NC group (Fig. 2A and B). In particular, the interference efficacy of si-RFC3-1 was more apparent than that of si-RFC3-2, and was thus applied to the subsequent experiments.

As determined by CCK-8 assay, SW620 cell viability was significantly suppressed by depletion of RFC3 (Fig. 2C). Also, the experimental data from EDU staining illuminated that the number of EDU-positive cells was reduced when RFC3 was downregulated (Fig. 2D). Furthermore, the effects of RFC3 on the apoptosis of SW620 cells were evaluated. By contrast, through flow cytometric analysis, it was revealed that RFC3 inhibition resulted in a significant increase in the apoptotic rate of SW620 cells (Fig. 3A and B). In addition, the expression levels of proteins involved in apoptosis were examined, and it was discovered that BCL2 expression was decreased, while Bax and Cleaved caspase3 expression levels were increased after RFC3 was depleted (Fig. 3C). To sum up, RFC3 interference protected against CRC cell proliferation and contributed to CRC cell apoptosis.

RFC3 depletion obstructs CRC cell migration, invasion and angiogenesis

Wound healing and Transwell assays were used to measure SW620 cell migration and invasion, respectively. The results revealed that the migratory and invasive capacities of SW620 cells were both significantly decreased by the depletion of RFC3 compared with the siRNA-NC (Fig. 4A and B). Western blotting also revealed that depletion of RFC3 significantly reduced the protein expression levels of metastasis-associated MMP2 and MMP9 compared with the siRNA-NC (Fig. 4C). Tube formation assays demonstrated that the tube formation capacity of HUVECs was attenuated in the CM from RFC3-silenced SW620 cells (Fig. 4D), which was accompanied by the significantly reduced protein expression levels of angiogenesis-related VEGF and VEGFR1 (Fig. 4E). Overall, RFC3-knockdown decreased the migration, invasion and angiogenesis of CRC cells.

RFC3 protein interacts with KIF14 protein

The Coexpedia and Biogrid databases were used predict the co-expression between RFC3 and KIF14. As predicted by the Coexpedia database, RFC3 and KIF14 were co-expressed (Fig. 5A). The potential binding of the RFC3 protein to the KIF14 protein was also shown in the Biogrid database (Fig. 5B). Additionally, TNMplot and GEPIA databases revealed that KIF14 expression was significantly upregulated in CRC tissues compared with the normal tissues (Fig. 5C-D). Higher KIF14 expression predicted the decreased survival in patients with CRC (Fig. 5E). Though western blotting, KIF14 protein expression was revealed to be significantly depleted after RFC3 was knocked down (Fig. 5F). The results of Co-IP revealed that both RFC3 and KIF14 were expressed in the input group. KIF14 protein was revealed to exist in the anti-RFC3 group and RFC3 protein was revealed to exist in the anti-KIF14 group. However, IgG could not pull down RFC3 and was used to rule out false-positive results. This suggested that RFC3 potentially interacted with KIF14 (Fig. 5G).

RFC3 insufficiency downregulates KIF14 to hamper CRC cell proliferation and exacerbate CRC cell apoptosis

With the aim of determining whether the interaction between RFC3 and KIF14 was involved in the progression of CRC, KIF14 expression was markedly increased after transfection with Ov-KIF14 (Fig. 6A and B). The results of the CCK-8 assay revealed that RFC3 depletion blocked the viability of SW620 cells, which was then improved after KIF14 was overexpressed (Fig. 6C). As illustrated in Fig. 6D, the suppressed SW620 cell proliferation induced by RFC3 interference was increased again when KIF14 was upregulated. Concurrently, the number of apoptotic SW620 cells was noticeably enhanced due to RFC3 inhibition, which was then reversed by KIF14 elevation (Fig. 7A and B). Similarly, the expression levels of BCL2, and the augmented expression levels of Bax and Cleaved caspase3 in RFC3-silenced SW620 cells were both reversed by upregulation of KIF14 (Fig. 7C). All of these results suggested that the effects of RFC3 knockdown on the proliferation and apoptosis of CRC cells were reversed by KIF14 elevation.

RFC3 insufficiency downregulates KIF14 to halt the migration, invasion and angiogenesis of CRC cells

Moreover, the restrained SW620 cell migration and invasion mediated by RFC3 depletion were facilitated again by overexpression of KIF14 (Fig. 8A and B), which was also evidenced by the increased expression levels of MMP2 and MMP9 in RFC3-silenced SW620 cells transfected with Ov-KIF14 (Fig. 8C). Furthermore, RFC3 downregulation reduced HUVECs tube formation, and depleted VEGF and VEGFR1 expression levels in the CM of SW620 cells, which was then partially restored by elevation of KIF14 (Fig. 8D and E). Taken together, the inhibitory role of RFC3 depletion in CRC cell migration, invasion and angiogenesis was counteracted by KIF14.


Metastasis and angiogenesis are considered the major drivers of CRC, which results from the transition of then normal colonic epithelium to adenoma (23,24). In addition, a stepwise accumulation of genetic and epigenetic alterations is involved in the process of CRC (25). In the present study, RFC3 expression was elevated in CRC cells, whereas RFC3 deficiency decreased the proliferation, migration, invasion and angiogenesis, while stimulating the apoptosis, of SW620 cells. Moreover, RFC3 was revealed to potentially interact with KIF14.

RFC family members have been demonstrated to participate in the biological behaviors of cancer cells, including CRC (26,27). Dysregulation of RFC3 has been detected in multiple tumors. For instance, RFC3 downregulation reduces the invasion, migration and epithelial-mesenchymal transition of lung adenocarcinoma and breast cancer cells (10,13). Lin et al elaborated that RFC3 is upregulated in CRC and RFC3 mutations may affect the outcome of patients with CRC (14). Consistent with this finding, RFC3 was revealed to be highly expressed in CRC cells in the current study. Functional experiments illuminated that after RFC3 was depleted following transfection with si-RFC3-1/2, the viability and proliferation of CRC cells were decreased, whereas the apoptosis of SW620 cells was aggravated, accompanied by a decrease in anti-apoptotic BCL2 expression and an increase in pro-apoptotic Bax and Cleaved caspase 3 expression. Knockdown of RFC3 resulted in a reduction in the migratory and invasive capacities, as well as the expression levels of metastasis-related MMP2 and MMP9 in SW620 cells.

Through supplying the blood with oxygen and nutrients dependent on new vessels, angiogenesis may exert a profound impact on the formation and progression of solid tumors (28). Besides, aberrant regulation of angiogenesis is deemed as one of the most significant mechanisms involved in tumor invasion and metastasis (29). VEGF represents a growth factor with important pro-angiogenic activity, which functions through binding with VEGFR1, a member of the VEGF family (30). High expression of VEGF and blood vessel formation are closely related to the invasion, metastasis and poor prognosis of CRC (31-33). In the present study, the impacts of RFC3 on angiogenesis in CRC were also assessed, and it was demonstrated that HUVEC tube formation was obstructed in the CM from SW620 cells transfected with si-RFC3, which was also evidenced by the decline in VEGF and VEGFR1 protein expression, suggesting the anti-angiogenic role of RFC3 absence in CRC.

Based on Coexpedia and Biogrid databases, RFC3 was predicted to be co-expressed with KIF14 and to bind with KIF14. As reported by Ji et al, KIF14 may be implicated in the miR-17-3p/PLCD1 regulatory process in colon cancer by interacting with the PLCD1 protein (34). Through the present investigation, it was revealed that KIF14 expression was also decreased when RFC3 was downregulated. Mechanistic assays also identified the binding of the RFC3 protein with the KIF14 protein. Inhibition of KIF14 has been supported to suppress angiogenesis in esophageal squamous cell carcinoma and glioma (35,36). Moreover, KIF14 expression is altered in CRC tissues and is associated with the clinical outcome of patients with CRC, as well as the cell cycle, DNA replication and DNA repair in CRC (37). Additionally, growing evidence has documented that KIF14 is overexpressed in CRC and acts as a tumor promoter by accelerating cell proliferation (21,34). The present study indicated that after KIF14 was overexpressed, the suppressive role of RFC3 deficiency in cell proliferation, migration, invasion and angiogenesis, and its stimulatory role in apoptosis in CRC were partially counteracted.

In conclusion, RFC3 exhibited increased expression in CRC cells and disruption of RFC3 may halt the development of CRC. To the best of our knowledge, this is the first report corroborating that RFC3 modulates the cellular events in CRC by interacting with KIF14. Therefore, RFC3 may function as a molecular marker for CRC and silencing RFC3 may be valued as a potential therapeutic modality for CRC. The present study only discussed the role of RFC3 and KIF14 in the malignant phenotypes of SW620 cells. The more CRC cell lines validation and further in vivo animal experiments will be performed in the future investigation to support the conclusion obtained in this study. In addition, the lack of a relationship between RFC3 expression levels and survival in patients with CRC is another limitation of the current study.


Not applicable.


Funding: No funding was received.

Authors' contributions

RY and XW were responsible for the methodology, data curation and writing the original draft preparation. FQ was responsible for the statistical analysis, validation and writing, reviewing and editing the manuscript. QY was responsible for the conceptualization, project administration, supervision and funding acquisition. All the authors read and approved the final manuscript. RY and QY confirm the authenticity of all the raw data.

Availability of data and material

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.



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Volume 27 Issue 5

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Yu R, Wu X, Qian F and Yang Q: RFC3 drives the proliferation, migration, invasion and angiogenesis of colorectal cancer cells by binding KIF14. Exp Ther Med 27: 222, 2024
Yu, R., Wu, X., Qian, F., & Yang, Q. (2024). RFC3 drives the proliferation, migration, invasion and angiogenesis of colorectal cancer cells by binding KIF14. Experimental and Therapeutic Medicine, 27, 222.
Yu, R., Wu, X., Qian, F., Yang, Q."RFC3 drives the proliferation, migration, invasion and angiogenesis of colorectal cancer cells by binding KIF14". Experimental and Therapeutic Medicine 27.5 (2024): 222.
Yu, R., Wu, X., Qian, F., Yang, Q."RFC3 drives the proliferation, migration, invasion and angiogenesis of colorectal cancer cells by binding KIF14". Experimental and Therapeutic Medicine 27, no. 5 (2024): 222.