Oral squamous cell carcinoma (OSCC) accounts for over 90% of all oral cancers and ranks as the sixth most common malignancy worldwide. Among OSCC subtypes, tongue squamous cell carcinoma (TSCC) is the most prevalent and aggressive. Currently, multidisciplinary sequential therapy centered on surgery remains the primary treatment strategy for OSCC. However, delayed diagnosis and high rates of postoperative recurrence and metastasis continue to limit overall treatment efficacy. Recent studies have shown that microRNAs (miRNAs) play pivotal roles in the regulation of tumor initiation and progression. Notably, miR-143 has been identified as a potential tumor suppressor. This study aimed to investigate the biological functions and molecular mechanisms of miR-143 in OSCC.CAL-27 cells were transfected with miR-143 mimics, and cell proliferation, colony formation, migration, and invasion were evaluated using Cell Counting Kit-8(CCK-8), colony formation, wound healing, and Transwell assays, respectively. Tumorigenicity in vivo was assessed using a xenograft model in nude mice. The expression of key components of the AKT/STAT3/NF-κB signaling pathway was examined by Western blotting and quantitative real-time PCR (qRT-PCR). The results demonstrated that miR-143 expression was significantly upregulated in transfected cells, resulting in reduced proliferative, migratory, and invasive capacities. In vivo experiments further confirmed the tumor-suppressive effect of miR-143, as evidenced by smaller tumor volumes in the treatment group. Mechanistically, miR-143 overexpression led to downregulation of p-AKT, p-STAT3, p-p65, and CDK2, and upregulation of E-cadherin. In conclusion, these findings indicate that miR-143 functions as a tumor suppressor in OSCC by inhibiting the AKT/STAT3/NF-κB pathway and promoting E-cadherin expression, suggesting its potential as a therapeutic target for oral cancer.

Shen Lu, Xu Ping. The Inhibition of Oral Squamous Cell Carcinoma Proliferation and Metastasis by MiR-143 through Modulation of the AKT/STAT3/NF-κB Signaling Pathway. Academic Journal of Medicine & Health Sciences (2025), Vol. 6, Issue 8: 1-10. https://doi.org/10.25236/AJMHS.2025.060801.

[1] KIJOWSKA J, GRZEGORCZYK J, GLIWA K, et al. Epidemiology, Diagnostics, and Therapy of Oral Cancer—Update Review[J]. Cancers, 2024, 16(18): 3156.

[2] AN Y, WANG Z, XU M, et al. Oral squamous cell carcinomas: state of the field and emerging directions[J]. International Journal of Oral Science, 2023, 15: 44. 

[3] ANNERTZ K, ANDERSON H, PALMÉR K, et al. The increase in incidence of cancer of the tongue in the Nordic countries continues into the twenty-first century[J]. Acta Oto-Laryngologica, 2012, 132(5): 552-557. 

[4] Brocklehurst PR, Baker S R, M Speight P. Oral cancer screening:what have we learnt and what is there still to achieve?[J]. Future Oncology,2010,6(2):99- 104.

[5] ALIM N, ELSHEIKH M, SATTI A A, et al. Recurrence of oral squamous cell carcinoma in surgically treated patients at Khartoum Teaching Dental Hospital retrospective cross-sectional study[J]. BMC Cancer, 2024, 24(1): 781. 

[6] Zamore PD. RNA interference:listening to the sound of silence[J]. Journal, 2001, 8(12): 746-750.

[7] Ketting R.F, Fischer, E.Bernstein et al. Dicer Functions in RNA Interference and in Synthesis of Small RNA Involved in Developmental Timing in C.elegans[J]. Journal, 2001, 15(20): 2654-2659.

[8] Florczuk M, Szpechcinski A, Chorostowska-Wynimko J. miRNAs as Biomarkers and Therapeutic Targets in Non-Small Cell Lung Cancer:Current Perspectives[J]. Targeted Oncology, 2017, 12(2): 179-200.

[9] Hunt S, Jones AV, Hinsley E E, et al. MicroRNA-124 suppresses oral squamo us cell carcinoma motility by targeting ITGB1[J]. FEBS letters, 2011, 585(1): 187-192.

[10] Zeng Q, Tao X, Huang F, et al. Overexpression of miR-155 promotes the proliferation and invasion of oral squamous carcinoma cells by regulating BCL6/cyclin D2[J]. International Journal of Molecular Medicine, 2016, 16(4): 59-69.

[11] Takagi T, Iio A , Nakagawa Y, et al. Decreased Expression of MicroRNA-143 and -145 in Human Gastric Cancers[J]. Oncology, 2009, 77(1): 12-21.

[12] Zhang Y, Wang Z, Chen M, et al. MicroRNA-143 Targets MACC1 to Inhibit Cell Invasion and Migration in Colorectal cancer[J]. Molecular Cancer, 2012, 11(1): 23-27.

[13] Kent O A, Fox-Talbot K, Halushka M K. RREB1 repressed miR-143/145 modulates KRAS signaling through downregulation of multiple targets[J]. Oncogene, 2012, 4(1): 23-27.

[14] Mayakannan M, Ganesan A, Ramamurthy R, et al. Down Regulation of miR-34a and miR-143 May Indirectly Inhibit p53 in Oral Squamous Cell Carcinoma: a Pilot Study[J]. Asian Pacific Journal of Cancer Prevention Apjcp, 2015, 16(17): 7619-7624.

[15] Sun X, Zhang L. MicroRNA-143 suppresses oral squamous cell carcinoma(OSCC) cell growth, invasion and glucose metabolism through targeting Hexokinase2[J]. Bioscience Reports, 2017, 18(15): 19-24.

[16] Mascitti M, Orsini G, Tosco V, et al. An Overview on Current Non-invasive Diagnostic Devices in Oral Oncology[J]. Frontiers in Physiology, 2018, 97(1): 154- 160.

[17] Heneghan H M, Miller N, Kerin M J. MiRNAs as biomarkers and therapeutic targets in cancer[J]. Current Opinion in Pharmacology, 2010, 10(5): 544-550.

[18] Esquela-Kerscher A, Slack. Oncomirs-microRNAs with a role in cancer[J]. Journal, 2016, 6(14): 259-269.

[19] Wei J, Ma Z, Li Y, et al. MiR-143 inhibits cell proliferation by targeting auto phagy-related 2B in non-small cell lung cancer H1299 cells[J]. Molecular Medicine Reports, 2014, 11(1): 229-233.

[20] Yi Qian, Yaoshu Teng, Yuandong Li, Xiaojiang Lin, Ming Guan, Yong Li, et al. MiR-143-3p suppresses the progression of nasal squamous cell carcinoma by targeting Bcl-2 and IGF1R[J]. Biochemical and biophysical research communications, 2019, 518(3): 492-499.

[21] Yang Guo, Ying Hu, Mingming Hu, et al. Long non-coding RNA ZEB2-AS1 promotes proliferation and inhibits apoptosis in human lung cancer cells[J].Oncology letters, 2018, 15(4): 5220-5226.

[22] Bufalino A, Cervigne N K, Oliveira C E D, et al. Low miR-143/miR-145 Cluster Levels Induce Activin A Overexpression in Oral Squamous Cell Carcinomas, Which Contributes to Poor Prognosis[J].PLOS ONE.2015, 10(8)599-604.

[23] Kiesslich T, Pichler M, Neureiter D. Epigenetic control of epithelial-mesenc hymal-transition in human cancer (Review)[J]. Molecular and Clinical Oncology, 2013, 1(1): 3- 11.

[24] Gheldof A, Berx G. Cadherins and epithelial-to-mesenchymal transition[J]. Progress in Molecular Biology & Translational Science, 2013, 116(16): 317-320.

[25] Puisieux A, Brabletz T, Caramel J. Oncogenic roles of EMT-inducing transcription factors[J]. Nature Cell Biology, 2014, 16(6): 488-494.

[26] MIHARA M, SHINTANI S, NAKAHARA Y, et al. Overexpression of CDK2 Is a Prognostic Indicator of Oral Cancer Progression[J]. Japanese Journal of Cancer Research : Gann, 2001, 92(3): 352-360. 

[27] PELLARIN I, DALL’ACQUA A, FAVERO A, et al. Cyclin-dependent protein kinases and cell cycle regulation in biology and disease[J]. Signal Transduction and Targeted Therapy, 2025, 10(1): 11.

[28] Wang F, Li L, Chen Z, et al. MicroRNA-214 acts as a potential oncogene in  breast cancer by targeting the PTEN-PI3K/Akt signaling pathway[J]. International Journal of Molecular Medicine, 2016. 14(10): 39-44.

[29] Ke K, Lou T. MicroRNA-10a suppresses breast cancer progression via PI3K/Akt/mTOR pathway[J]. Oncology Letters, 2017, 30(14): 30-34.

[30] He W, Cheng Y. Inhibition of miR-20 promotes proliferation and autophagy in articular chondrocytes by PI3K/AKT/mTOR signaling pathway[J].Biomedecine & pharmacotherapie, 2017, 9(14): 607-615.

[31] Qiang W, Shennan J, Yan J, et al. SSRP1 influences colorectal cancer cell growth and apoptosis via the AKT pathway[J]. Journal, 2019, 16(4): 1573- 1582.

[32] Jiang B H, Liu L Z. PI3K/PTEN signaling in tumorigenesis and angiogenesis[J]. Biochim Biophys Acta, 2008, 1784(1): 150- 158.

[33] Wang B, Wang H, Yang Z. MiR-122 Inhibits Cell Proliferation and Tumorigenesis of Breast Cancer by Targeting IGF1R[J]. PLOS ONE, 2012, 7(8): 41-49.

[34] Cui W, Zhang S, Shan C, Zhou L, Zhou Z. microRNA-133a regulates the cell cycle and proliferation of breast cancer cells by targeting epidermal growth factor receptor through the EGFR/Akt signaling pathway[J]. FEBS Journal, 2013, 280(16): 3962-3974.

[35] Rawlings, J. S. The JAK/STAT signaling pathway[J]. Journal of Cell Science, 2004, 117(8): 1281- 1283.

[36] HU Y, DONG Z, LIU K. Unraveling the complexity of STAT3 in cancer: molecular understanding and drug discovery[J]. Journal of Experimental & Clinical Cancer Research, 2024, 43(1): 23. 

[37] Beiqin Yu, Xin Lv, Liping Su, Jianfang Li, Yingyan Yu, Qinlong Gu, et al. MiR-148a Functions as a Tumor Suppressor by Targeting CCK-BR via Inactivating STAT3 and Akt in Human Gastric Cancer[J]. PloS one, 2016, 11(8): 961-970.

[38] Fan Z, Cui H, Yu H, et al. MiR-125a promotes paclitaxel sensitivity in cervical cancer through altering STAT3 expression[J]. Oncogenesis, 2016, 5(2): 197-203.

[39] MAO H, ZHAO X, SUN S. NF-κB in inflammation and cancer[J]. Cellular & Molecular Immunology, 2025, 22(8): 811-839. 

[40] WU X, SUN L, XU F. NF-κB in Cell Deaths, Therapeutic Resistance and Nanotherapy of Tumors: Recent Advances[J]. Pharmaceuticals, 2023, 16(6): 783. 

[41] MA Q, HAO S, HONG W, et al. Versatile function of NF-ĸB in inflammation and cancer[J/OL]. Experimental Hematology & Oncology, 2024, 13(1): 68. 

[42] CAO Y, YI Y, HAN C, et al. NF-κB signaling pathway in tumor microenvironment[J]. Frontiers in Immunology,2024.1476030.