Modulating Colorectal Cancer Cell Propagation and Immune Evasion by miRNA-148a-3p via KLF4
Abstract
MicroRNA (miR)-148a-3p is most frequently upregulated in solid tumors, such as colorectal cancer (CRC). This study aimed to elucidate the role of miR-148a-3p in CRC cell proliferation and immune escape and its potential mechanism.
miR-148a-3p and Kruppel-like transcription factor 4 (KLF4) expressions were quantified by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and immune evasion abilities of CRC cells were evaluated with the cell counting kit-8 assay, Transwell, western blot, and enzyme-linked immunosorbent assays. The proliferation or apoptosis of CD8+ and CD4+ T cells after coculture with CRC cells was assessed by flow cytometry. Dual-luciferase reporter gene testing was used to validate the targeting association between KLF4 and miR-148a-3p. A nude mouse subcutaneous graft tumor model was constructed, and CD8+ T cell infiltration was detected by immunohistochemistry and flow cytometry.
miR-148a-3p exhibited a high level, while KLF4 was under-expressed in CRC cells; miR-148a-3p negatively regulated the KLF4 level. Overexpression of miR-148a-3p enhanced CRC cell proliferation, migration, invasion, EMT, and immune escape; silencing miR-148a-3p caused the opposite trend; moreover, the said biological functions of CRC cells were weakened with overexpression of KLF4 but enhanced with silencing of KLF4; silencing KLF4 weakened the influences of dampened miR-148a-3p on CRC development. Silencing miR-148a-3p promoted the infiltration of CD8+ T cells and inhibited tumor growth.
In summary, miR-148a-3p promotes CRC cell proliferation and immune evasion by regulating the expression of KLF4. This finding can be used for reference when developing a new way of CRC treatment.
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2. Phang CW, Karsani SA, Abd Malek SN. Induction of Apoptosis and Cell Cycle Arrest by Flavokawain C on HT-29 Human Colon Adenocarcinoma via Enhancement of Reactive Oxygen Species Generation, Upregulation of p21, p27, and GADD153, and Inactivation of Inhibitor of Apoptosis Proteins. Pharmacogn Mag. 2017;13(Suppl 2):S321-S8.
3. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49.
4. Xia C, Dong X, Li H, Cao M, Sun D, He S, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl). 2022;135(5):584-90.
5. Loree JM, Kopetz S. Recent developments in the treatment of metastatic colorectal cancer. Ther Adv Med Oncol. 2017;9(8):551-64.
6. Li Y, He M, Zhou Y, Yang C, Wei S, Bian X, et al. The Prognostic and Clinicopathological Roles of PD-L1 Expression in Colorectal Cancer: A Systematic Review and Meta-Analysis. Front Pharmacol. 2019;10:139.
7. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17-48.
8. Sadri F, Rezaei Z. Noncoding RNAs: Key Modulators of the Hippo Pathway in Hepatocellular Carcinoma Progression. J Can Biomol Therap. 2025;2(1):73-88.
9. Zhao R, Zhao D, Zhu X, Li F, Xiong P, Li S, et al. The Influence of miR-3149 on the Malignancy Progression of Gastric Cancer by Negatively Regulating CEACAM5. J Can Biomol Therap. 2024;1(1):1-10.
10. Liu L, Wang Q, Qiu Z, Kang Y, Liu J, Ning S, et al. Noncoding RNAs: the shot callers in tumor immune escape. Signal Transduct Target Ther. 2020;5(1):102.
11. Omar HA, El-Serafi AT, Hersi F, Arafa EA, Zaher DM, Madkour M, et al. Immunomodulatory MicroRNAs in cancer: targeting immune checkpoints and the tumor microenvironment. FEBS J. 2019;286(18):3540-57.
12. Yi M, Xu L, Jiao Y, Luo S, Li A, Wu K. The role of cancer-derived microRNAs in cancer immune escape. J Hematol Oncol. 2020;13(1):25.
13. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004;101(9):2999-3004.
14. Lin S, Gregory RI. MicroRNA biogenesis pathways in cancer. Nat Rev Cancer. 2015;15(6):321-33.
15. Ye Z, Jiang Y, Wu J. A novel necroptosis-associated miRNA signature predicting prognosis of endometrial cancer and correlated with immune infiltration. Taiwan J Obstet Gynecol. 2023;62(2):291-8.
16. Cao Y, Jiao N, Sun T, Ma Y, Zhang X, Chen H, et al. CXCL11 Correlates With Antitumor Immunity and an Improved Prognosis in Colon Cancer. Front Cell Dev Biol. 2021;9:646252.
17. Chen X, Wang YW, Gao P. SPIN1, negatively regulated by miR-148/152, enhances Adriamycin resistance via upregulating drug metabolizing enzymes and transporter in breast cancer. J Exp Clin Cancer Res. 2018;37(1):100.
18. Dawood AA, Saleh AA, Elbahr O, Gohar SF, Habieb MS. Inverse relationship between the level of miRNA 148a-3p and both TGF-beta1 and FIB-4 in hepatocellular carcinoma. Biochem Biophys Rep. 2021;27:101082.
19. Idichi T, Seki N, Kurahara H, Fukuhisa H, Toda H, Shimonosono M, et al. Molecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger strand of pre-miR-148a on gene regulation. Cancer Sci. 2018;109(6):2013-26.
20. Jung KH, Zhang J, Zhou C, Shen H, Gagea M, Rodriguez-Aguayo C, et al. Differentiation therapy for hepatocellular carcinoma: Multifaceted effects of miR-148a on tumor growth and phenotype and liver fibrosis. Hepatology. 2016;63(3):864-79.
21. Komatsu S, Imamura T, Kiuchi J, Takashima Y, Kamiya H, Ohashi T, et al. Depletion of tumor suppressor miRNA-148a in plasma relates to tumor progression and poor outcomes in gastric cancer. Am J Cancer Res. 2021;11(12):6133-46.
22. Wang W, Dong J, Wang M, Yao S, Tian X, Cui X, et al. miR-148a-3p suppresses epithelial ovarian cancer progression primarily by targeting c-Met. Oncol Lett. 2018;15(5):6131-6.
23. Mreich E, Chen XM, Zaky A, Pollock CA, Saad S. The role of Kruppel-like factor 4 in transforming growth factor-beta-induced inflammatory and fibrotic responses in human proximal tubule cells. Clin Exp Pharmacol Physiol. 2015;42(6):680-6.
24. Sevilla LM, Latorre V, Carceller E, Boix J, Vodak D, Mills IG, et al. Glucocorticoid receptor and Klf4 co-regulate anti-inflammatory genes in keratinocytes. Mol Cell Endocrinol. 2015;412:281-9.
25. Zahlten J, Herta T, Kabus C, Steinfeldt M, Kershaw O, Garcia P, et al. Role of Pneumococcal Autolysin for KLF4 Expression and Chemokine Secretion in Lung Epithelium. Am J Respir Cell Mol Biol. 2015;53(4):544-54.
26. Nah J, Seong RH. Kruppel-like factor 4 regulates the cytolytic effector function of exhausted CD8 T cells. Sci Adv. 2022;8(47):eadc9346.
27. Dong M, Xie Y, Xu Y. miR-7-5p regulates the proliferation and migration of colorectal cancer cells by negatively regulating the expression of Kruppel-like factor 4. Oncol Lett. 2019;17(3):3241-6.
28. Lv H, Zhang Z, Wang Y, Li C, Gong W, Wang X. MicroRNA-92a Promotes Colorectal Cancer Cell Growth and Migration by Inhibiting KLF4. Oncol Res. 2016;23(6):283-90.
29. Mao Q, Quan T, Luo B, Guo X, Liu L, Zheng Q. MiR-375 targets KLF4 and impacts the proliferation of colorectal carcinoma. Tumour Biol. 2016;37(1):463-71.
30. Shang Y, Zhu Z, Zhang Y, Ji F, Zhu L, Liu M, et al. MiR-7-5p/KLF4 signaling inhibits stemness and radioresistance in colorectal cancer. Cell Death Discov. 2023;9(1):42.
31. Zhai F, Cao C, Zhang L, Zhang J. miR-543 promotes colorectal cancer proliferation and metastasis by targeting KLF4. Oncotarget. 2017;8(35):59246-56.
32. Zhao W, Hisamuddin IM, Nandan MO, Babbin BA, Lamb NE, Yang VW. Identification of Kruppel-like factor 4 as a potential tumor suppressor gene in colorectal cancer. Oncogene. 2004;23(2):395-402.
33. Zhang C, Zhang C, Liu X, Sun W, Liu H. Circular RNA PGPEP1 induces colorectal cancer malignancy and immune escape. Cell cycle (Georgetown, Tex). 2023;22(14-16):1743-58.
34. Zheng J, Yang T, Gao S, Cheng M, Shao Y, Xi Y, et al. miR-148a-3p silences the CANX/MHC-I pathway and impairs CD8(+) T cell-mediated immune attack in colorectal cancer. FASEB J. 2021;35(8):e21776.
35. Felekkis K, Touvana E, Stefanou C, Deltas C. microRNAs: a newly described class of encoded molecules that play a role in health and disease. Hippokratia. 2010;14(4):236-40.
36. Ghaleb AM, Yang VW. Kruppel-like factor 4 (KLF4): What we currently know. Gene. 2017;611:27-37.
37. Ghaleb AM, McConnell BB, Kaestner KH, Yang VW. Altered intestinal epithelial homeostasis in mice with intestine-specific deletion of the Kruppel-like factor 4 gene. Dev Biol. 2011;349(2):310-20.
38. Feng F, Liu H, Chen A, Xia Q, Zhao Y, Jin X, et al. miR-148-3p and miR-152-3p synergistically regulate prostate cancer progression via repressing KLF4. J Cell Biochem. 2019;120(10):17228-39.
39. He Z, He J, Xie K. KLF4 transcription factor in tumorigenesis. Cell Death Discov. 2023;9(1):118.
40. Hu D, Gur M, Zhou Z, Gamper A, Hung MC, Fujita N, et al. Interplay between arginine methylation and ubiquitylation regulates KLF4-mediated genome stability and carcinogenesis. Nat Commun. 2015;6:8419.
41. Jiang Z, Zhang Y, Chen X, Wu P, Chen D. Long non-coding RNA LINC00673 silencing inhibits proliferation and drug resistance of prostate cancer cells via decreasing KLF4 promoter methylation. J Cell Mol Med. 2020;24(2):1878-92.
42. Leng Z, Li Y, Zhou G, Lv X, Ai W, Li J, et al. Kruppel-like factor 4 regulates stemness and mesenchymal properties of colorectal cancer stem cells through the TGF-beta1/Smad/snail pathway. J Cell Mol Med. 2020;24(2):1866-77.
43. Qiu Z, Tu L, Hu X, Zhou Z, Lin Y, Ye L, et al. A Preliminary Study of miR-144 Inhibiting the Stemness of Colon Cancer Stem Cells by Targeting Kruppel-Like Factor 4. J Biomed Nanotechnol. 2020;16(7):1102-9.
44. Tian Y, Luo A, Cai Y, Su Q, Ding F, Chen H, et al. MicroRNA-10b promotes migration and invasion through KLF4 in human esophageal cancer cell lines. J Biol Chem. 2010;285(11):7986-94.
45. Wei D, Wang L, Yan Y, Jia Z, Gagea M, Li Z, et al. KLF4 Is Essential for Induction of Cellular Identity Change and Acinar-to-Ductal Reprogramming during Early Pancreatic Carcinogenesis. Cancer Cell. 2016;29(3):324-38.
46. Xue M, Zhou C, Zheng Y, Zhang Z, Wang S, Fu Y, et al. The association between KLF4 as a tumor suppressor and the prognosis of hepatocellular carcinoma after curative resection. Aging (Albany NY). 2020;12(15):15566-80.
47. Zhang C, Liu J, Zhang Y, Luo C, Zhu T, Zhang R, et al. LINC01210 accelerates proliferation, invasion and migration in ovarian cancer through epigenetically downregulating KLF4. Biomed Pharmacother. 2019;119:109431.
48. Zhang N, Zhang J, Shuai L, Zha L, He M, Huang Z, et al. Kruppel-like factor 4 negatively regulates beta-catenin expression and inhibits the proliferation, invasion and metastasis of gastric cancer. Int J Oncol. 2012;40(6):2038-48.
49. Patel NV, Ghaleb AM, Nandan MO, Yang VW. Expression of the tumor suppressor Kruppel-like factor 4 as a prognostic predictor for colon cancer. Cancer Epidemiol Biomarkers Prev. 2010;19(10):2631-8.
50. Hu W, Hofstetter WL, Li H, Zhou Y, He Y, Pataer A, et al. Putative tumor-suppressive function of Kruppel-like factor 4 in primary lung carcinoma. Clin Cancer Res. 2009;15(18):5688-95.
51. Zhou Y, Hofstetter WL, He Y, Hu W, Pataer A, Wang L, et al. KLF4 inhibition of lung cancer cell invasion by suppression of SPARC expression. Cancer Biol Ther. 2010;9(7):507-13.
52. Dong P, Kaneuchi M, Watari H, Hamada J, Sudo S, Ju J, et al. MicroRNA-194 inhibits epithelial to mesenchymal transition of endometrial cancer cells by targeting oncogene BMI-1. Mol Cancer. 2011;10:99.
53. Kumar M, Allison DF, Baranova NN, Wamsley JJ, Katz AJ, Bekiranov S, et al. NF-kappaB regulates mesenchymal transition for the induction of non-small cell lung cancer initiating cells. PLoS One. 2013;8(7):e68597.
54. Dongre A, Weinberg RA. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol. 2019;20(2):69-84.
55. Mittal V. Epithelial Mesenchymal Transition in Tumor Metastasis. Annu Rev Pathol. 2018;13:395-412.
56. Reiser J, Banerjee A. Effector, Memory, and Dysfunctional CD8(+) T Cell Fates in the Antitumor Immune Response. J Immunol Res. 2016;2016:8941260.
57. Zeng Z, Chew HY, Cruz JG, Leggatt GR, Wells JW. Investigating T Cell Immunity in Cancer: Achievements and Prospects. Int J Mol Sci. 2021;22(6).
58. Chen Y, Xu J, Wu X, Yao H, Yan Z, Guo T, et al. CD147 regulates antitumor CD8(+) T-cell responses to facilitate tumor-immune escape. Cell Mol Immunol. 2021;18(8):1995-2009.
59. Jansen CS, Prokhnevska N, Master VA, Sanda MG, Carlisle JW, Bilen MA, et al. An intra-tumoral niche maintains and differentiates stem-like CD8 T cells. Nature. 2019;576(7787):465-70.
60. Jhunjhunwala S, Hammer C, Delamarre L. Antigen presentation in cancer: insights into tumour immunogenicity and immune evasion. Nat Rev Cancer. 2021;21(5):298-312.
61. Shi Z, Du Q, Wang X, Wang J, Chen H, Lang Y, et al. Granzyme B in circulating CD8+ T cells as a biomarker of immunotherapy effectiveness and disability in neuromyelitis optica spectrum disorders. Front Immunol. 2022;13:1027158.
2. Phang CW, Karsani SA, Abd Malek SN. Induction of Apoptosis and Cell Cycle Arrest by Flavokawain C on HT-29 Human Colon Adenocarcinoma via Enhancement of Reactive Oxygen Species Generation, Upregulation of p21, p27, and GADD153, and Inactivation of Inhibitor of Apoptosis Proteins. Pharmacogn Mag. 2017;13(Suppl 2):S321-S8.
3. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-49.
4. Xia C, Dong X, Li H, Cao M, Sun D, He S, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl). 2022;135(5):584-90.
5. Loree JM, Kopetz S. Recent developments in the treatment of metastatic colorectal cancer. Ther Adv Med Oncol. 2017;9(8):551-64.
6. Li Y, He M, Zhou Y, Yang C, Wei S, Bian X, et al. The Prognostic and Clinicopathological Roles of PD-L1 Expression in Colorectal Cancer: A Systematic Review and Meta-Analysis. Front Pharmacol. 2019;10:139.
7. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17-48.
8. Sadri F, Rezaei Z. Noncoding RNAs: Key Modulators of the Hippo Pathway in Hepatocellular Carcinoma Progression. J Can Biomol Therap. 2025;2(1):73-88.
9. Zhao R, Zhao D, Zhu X, Li F, Xiong P, Li S, et al. The Influence of miR-3149 on the Malignancy Progression of Gastric Cancer by Negatively Regulating CEACAM5. J Can Biomol Therap. 2024;1(1):1-10.
10. Liu L, Wang Q, Qiu Z, Kang Y, Liu J, Ning S, et al. Noncoding RNAs: the shot callers in tumor immune escape. Signal Transduct Target Ther. 2020;5(1):102.
11. Omar HA, El-Serafi AT, Hersi F, Arafa EA, Zaher DM, Madkour M, et al. Immunomodulatory MicroRNAs in cancer: targeting immune checkpoints and the tumor microenvironment. FEBS J. 2019;286(18):3540-57.
12. Yi M, Xu L, Jiao Y, Luo S, Li A, Wu K. The role of cancer-derived microRNAs in cancer immune escape. J Hematol Oncol. 2020;13(1):25.
13. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004;101(9):2999-3004.
14. Lin S, Gregory RI. MicroRNA biogenesis pathways in cancer. Nat Rev Cancer. 2015;15(6):321-33.
15. Ye Z, Jiang Y, Wu J. A novel necroptosis-associated miRNA signature predicting prognosis of endometrial cancer and correlated with immune infiltration. Taiwan J Obstet Gynecol. 2023;62(2):291-8.
16. Cao Y, Jiao N, Sun T, Ma Y, Zhang X, Chen H, et al. CXCL11 Correlates With Antitumor Immunity and an Improved Prognosis in Colon Cancer. Front Cell Dev Biol. 2021;9:646252.
17. Chen X, Wang YW, Gao P. SPIN1, negatively regulated by miR-148/152, enhances Adriamycin resistance via upregulating drug metabolizing enzymes and transporter in breast cancer. J Exp Clin Cancer Res. 2018;37(1):100.
18. Dawood AA, Saleh AA, Elbahr O, Gohar SF, Habieb MS. Inverse relationship between the level of miRNA 148a-3p and both TGF-beta1 and FIB-4 in hepatocellular carcinoma. Biochem Biophys Rep. 2021;27:101082.
19. Idichi T, Seki N, Kurahara H, Fukuhisa H, Toda H, Shimonosono M, et al. Molecular pathogenesis of pancreatic ductal adenocarcinoma: Impact of passenger strand of pre-miR-148a on gene regulation. Cancer Sci. 2018;109(6):2013-26.
20. Jung KH, Zhang J, Zhou C, Shen H, Gagea M, Rodriguez-Aguayo C, et al. Differentiation therapy for hepatocellular carcinoma: Multifaceted effects of miR-148a on tumor growth and phenotype and liver fibrosis. Hepatology. 2016;63(3):864-79.
21. Komatsu S, Imamura T, Kiuchi J, Takashima Y, Kamiya H, Ohashi T, et al. Depletion of tumor suppressor miRNA-148a in plasma relates to tumor progression and poor outcomes in gastric cancer. Am J Cancer Res. 2021;11(12):6133-46.
22. Wang W, Dong J, Wang M, Yao S, Tian X, Cui X, et al. miR-148a-3p suppresses epithelial ovarian cancer progression primarily by targeting c-Met. Oncol Lett. 2018;15(5):6131-6.
23. Mreich E, Chen XM, Zaky A, Pollock CA, Saad S. The role of Kruppel-like factor 4 in transforming growth factor-beta-induced inflammatory and fibrotic responses in human proximal tubule cells. Clin Exp Pharmacol Physiol. 2015;42(6):680-6.
24. Sevilla LM, Latorre V, Carceller E, Boix J, Vodak D, Mills IG, et al. Glucocorticoid receptor and Klf4 co-regulate anti-inflammatory genes in keratinocytes. Mol Cell Endocrinol. 2015;412:281-9.
25. Zahlten J, Herta T, Kabus C, Steinfeldt M, Kershaw O, Garcia P, et al. Role of Pneumococcal Autolysin for KLF4 Expression and Chemokine Secretion in Lung Epithelium. Am J Respir Cell Mol Biol. 2015;53(4):544-54.
26. Nah J, Seong RH. Kruppel-like factor 4 regulates the cytolytic effector function of exhausted CD8 T cells. Sci Adv. 2022;8(47):eadc9346.
27. Dong M, Xie Y, Xu Y. miR-7-5p regulates the proliferation and migration of colorectal cancer cells by negatively regulating the expression of Kruppel-like factor 4. Oncol Lett. 2019;17(3):3241-6.
28. Lv H, Zhang Z, Wang Y, Li C, Gong W, Wang X. MicroRNA-92a Promotes Colorectal Cancer Cell Growth and Migration by Inhibiting KLF4. Oncol Res. 2016;23(6):283-90.
29. Mao Q, Quan T, Luo B, Guo X, Liu L, Zheng Q. MiR-375 targets KLF4 and impacts the proliferation of colorectal carcinoma. Tumour Biol. 2016;37(1):463-71.
30. Shang Y, Zhu Z, Zhang Y, Ji F, Zhu L, Liu M, et al. MiR-7-5p/KLF4 signaling inhibits stemness and radioresistance in colorectal cancer. Cell Death Discov. 2023;9(1):42.
31. Zhai F, Cao C, Zhang L, Zhang J. miR-543 promotes colorectal cancer proliferation and metastasis by targeting KLF4. Oncotarget. 2017;8(35):59246-56.
32. Zhao W, Hisamuddin IM, Nandan MO, Babbin BA, Lamb NE, Yang VW. Identification of Kruppel-like factor 4 as a potential tumor suppressor gene in colorectal cancer. Oncogene. 2004;23(2):395-402.
33. Zhang C, Zhang C, Liu X, Sun W, Liu H. Circular RNA PGPEP1 induces colorectal cancer malignancy and immune escape. Cell cycle (Georgetown, Tex). 2023;22(14-16):1743-58.
34. Zheng J, Yang T, Gao S, Cheng M, Shao Y, Xi Y, et al. miR-148a-3p silences the CANX/MHC-I pathway and impairs CD8(+) T cell-mediated immune attack in colorectal cancer. FASEB J. 2021;35(8):e21776.
35. Felekkis K, Touvana E, Stefanou C, Deltas C. microRNAs: a newly described class of encoded molecules that play a role in health and disease. Hippokratia. 2010;14(4):236-40.
36. Ghaleb AM, Yang VW. Kruppel-like factor 4 (KLF4): What we currently know. Gene. 2017;611:27-37.
37. Ghaleb AM, McConnell BB, Kaestner KH, Yang VW. Altered intestinal epithelial homeostasis in mice with intestine-specific deletion of the Kruppel-like factor 4 gene. Dev Biol. 2011;349(2):310-20.
38. Feng F, Liu H, Chen A, Xia Q, Zhao Y, Jin X, et al. miR-148-3p and miR-152-3p synergistically regulate prostate cancer progression via repressing KLF4. J Cell Biochem. 2019;120(10):17228-39.
39. He Z, He J, Xie K. KLF4 transcription factor in tumorigenesis. Cell Death Discov. 2023;9(1):118.
40. Hu D, Gur M, Zhou Z, Gamper A, Hung MC, Fujita N, et al. Interplay between arginine methylation and ubiquitylation regulates KLF4-mediated genome stability and carcinogenesis. Nat Commun. 2015;6:8419.
41. Jiang Z, Zhang Y, Chen X, Wu P, Chen D. Long non-coding RNA LINC00673 silencing inhibits proliferation and drug resistance of prostate cancer cells via decreasing KLF4 promoter methylation. J Cell Mol Med. 2020;24(2):1878-92.
42. Leng Z, Li Y, Zhou G, Lv X, Ai W, Li J, et al. Kruppel-like factor 4 regulates stemness and mesenchymal properties of colorectal cancer stem cells through the TGF-beta1/Smad/snail pathway. J Cell Mol Med. 2020;24(2):1866-77.
43. Qiu Z, Tu L, Hu X, Zhou Z, Lin Y, Ye L, et al. A Preliminary Study of miR-144 Inhibiting the Stemness of Colon Cancer Stem Cells by Targeting Kruppel-Like Factor 4. J Biomed Nanotechnol. 2020;16(7):1102-9.
44. Tian Y, Luo A, Cai Y, Su Q, Ding F, Chen H, et al. MicroRNA-10b promotes migration and invasion through KLF4 in human esophageal cancer cell lines. J Biol Chem. 2010;285(11):7986-94.
45. Wei D, Wang L, Yan Y, Jia Z, Gagea M, Li Z, et al. KLF4 Is Essential for Induction of Cellular Identity Change and Acinar-to-Ductal Reprogramming during Early Pancreatic Carcinogenesis. Cancer Cell. 2016;29(3):324-38.
46. Xue M, Zhou C, Zheng Y, Zhang Z, Wang S, Fu Y, et al. The association between KLF4 as a tumor suppressor and the prognosis of hepatocellular carcinoma after curative resection. Aging (Albany NY). 2020;12(15):15566-80.
47. Zhang C, Liu J, Zhang Y, Luo C, Zhu T, Zhang R, et al. LINC01210 accelerates proliferation, invasion and migration in ovarian cancer through epigenetically downregulating KLF4. Biomed Pharmacother. 2019;119:109431.
48. Zhang N, Zhang J, Shuai L, Zha L, He M, Huang Z, et al. Kruppel-like factor 4 negatively regulates beta-catenin expression and inhibits the proliferation, invasion and metastasis of gastric cancer. Int J Oncol. 2012;40(6):2038-48.
49. Patel NV, Ghaleb AM, Nandan MO, Yang VW. Expression of the tumor suppressor Kruppel-like factor 4 as a prognostic predictor for colon cancer. Cancer Epidemiol Biomarkers Prev. 2010;19(10):2631-8.
50. Hu W, Hofstetter WL, Li H, Zhou Y, He Y, Pataer A, et al. Putative tumor-suppressive function of Kruppel-like factor 4 in primary lung carcinoma. Clin Cancer Res. 2009;15(18):5688-95.
51. Zhou Y, Hofstetter WL, He Y, Hu W, Pataer A, Wang L, et al. KLF4 inhibition of lung cancer cell invasion by suppression of SPARC expression. Cancer Biol Ther. 2010;9(7):507-13.
52. Dong P, Kaneuchi M, Watari H, Hamada J, Sudo S, Ju J, et al. MicroRNA-194 inhibits epithelial to mesenchymal transition of endometrial cancer cells by targeting oncogene BMI-1. Mol Cancer. 2011;10:99.
53. Kumar M, Allison DF, Baranova NN, Wamsley JJ, Katz AJ, Bekiranov S, et al. NF-kappaB regulates mesenchymal transition for the induction of non-small cell lung cancer initiating cells. PLoS One. 2013;8(7):e68597.
54. Dongre A, Weinberg RA. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol. 2019;20(2):69-84.
55. Mittal V. Epithelial Mesenchymal Transition in Tumor Metastasis. Annu Rev Pathol. 2018;13:395-412.
56. Reiser J, Banerjee A. Effector, Memory, and Dysfunctional CD8(+) T Cell Fates in the Antitumor Immune Response. J Immunol Res. 2016;2016:8941260.
57. Zeng Z, Chew HY, Cruz JG, Leggatt GR, Wells JW. Investigating T Cell Immunity in Cancer: Achievements and Prospects. Int J Mol Sci. 2021;22(6).
58. Chen Y, Xu J, Wu X, Yao H, Yan Z, Guo T, et al. CD147 regulates antitumor CD8(+) T-cell responses to facilitate tumor-immune escape. Cell Mol Immunol. 2021;18(8):1995-2009.
59. Jansen CS, Prokhnevska N, Master VA, Sanda MG, Carlisle JW, Bilen MA, et al. An intra-tumoral niche maintains and differentiates stem-like CD8 T cells. Nature. 2019;576(7787):465-70.
60. Jhunjhunwala S, Hammer C, Delamarre L. Antigen presentation in cancer: insights into tumour immunogenicity and immune evasion. Nat Rev Cancer. 2021;21(5):298-312.
61. Shi Z, Du Q, Wang X, Wang J, Chen H, Lang Y, et al. Granzyme B in circulating CD8+ T cells as a biomarker of immunotherapy effectiveness and disability in neuromyelitis optica spectrum disorders. Front Immunol. 2022;13:1027158.
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How to Cite
1.
Zhang C, Yi S, Cao X, Wang J. Modulating Colorectal Cancer Cell Propagation and Immune Evasion by miRNA-148a-3p via KLF4. Iran J Allergy Asthma Immunol. 2025;:1-17.
