Advances in study of non-coding RNA in pathogenesis of hepatocellular carcinoma and mechanism of sorafenib resistance in hepatocellular carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

FENG Haonan ¹ , LI Ziyi ² ,  TAN Gang ¹

1. Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, P. R. China;
2. Hepatosplenic Surgery Center, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, P. R. China;

Corresponding author：

TAN Gang, Email: ttgg4698@sina.com

Keywords：

hepatocellular carcinoma; non-coding RNA; sorafenib resistance; regulatory mechanism

DOI：

10.7507/1007-9424.201910093

Video：

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Objective To investigate the role of non-coding RNA (ncRNA) in the proliferation, migration and metastasis of hepatocellular carcinoma (HCC) and the mechanism of HCC resistance to sorafenib.Method The literatures of ncRNA studies related to the incidence of HCC in recent years were reviewed, and the relationship between different ncRNAs and the proliferation, migration and metastasis of HCC was summarized, and the mechanism of sorafenib resistance in the HCC was analyzed from the perspective of ncRNA.Results There were many kinds of ncRNAs, which were classified into the long ncRNA and short ncRNA according to their length. Currently, microRNA, which was widely studied, belonged to the short ncRNA. The regulation of the expressions of different microRNAs and long ncRNA could enhance or inhibit the signaling pathway of the producing HCC and played an important guiding role in the diagnosis and treatment of HCC. Meanwhile, the targeted regulation of this ncRNA could reverse the sorafenib resistance in the HCC.Conclusions ncRNA plays an important role in the pathogenesis of HCC and has become a potential target for the treatment of HCC. Targeted regulation of specific ncRNA expression could reverse sorafenib resistance in HCC.

Citation： FENG Haonan, LI Ziyi, TAN Gang. Advances in study of non-coding RNA in pathogenesis of hepatocellular carcinoma and mechanism of sorafenib resistance in hepatocellular carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2020, 27(7): 912-916. doi: 10.7507/1007-9424.201910093 Copy

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2.	Wang P, Tan G, Zhu M, et al. Hand-foot skin reaction is a beneficial indicator of sorafenib therapy for patients with hepatocellular carcinoma: a systemic review and meta-analysis. Expert Rev Gastroenterol Hepatol, 2018, 12(1): 1-8.
3.	Gezer U, Özgür E, Cetinkaya M, et al. Long non-coding RNAs with low expression levels in cells are enriched in secreted exosomes. Cell Biol Int, 2014, 38(9): 1076-1079.
4.	Skuratovskaia D, Vulf M, Komar A, et al. Promising directions in atherosclerosis treatment based on epigenetic regulation using microRNAs and long noncoding RNAs. Biomolecules, 2019, 9(6): pii: E226.
5.	Chen W, Liu D, Li QZ, et al. The function of ncRNAs in rheumatic diseases. Epigenomics, 2019, 11(7): 821-833.
6.	Wang Y, Chen F, Zhao M, et al. The long noncoding RNA HULC promotes liver cancer by increasing the expression of the HMGA2 oncogene via sequestration of the microRNA-186. J Biol Chem, 2017, 292(37): 15395-15407.
7.	Braicu C, Zimta AA, Harangus A, et al. The function of non-coding RNAs in lung cancer tumorigenesis. Cancers (Basel), 2019, 11(5): pii: E605.
8.	Huang W, Su G, Huang X, et al. Long noncoding RNA PCAT6 inhibits colon cancer cell apoptosis by regulating anti-apoptotic protein ARC expression via EZH2. Cell Cycle, 2019, 18(1): 69-83.
9.	Zhang J, Shi K, Huang W, et al. The DNA methylation profile of non-coding RNAs improves prognosis prediction for pancreatic adenocarcinoma. Cancer Cell Int, 2019, 19: 107.
10.	Michlewski G, Cáceres JF. Post-transcriptional control of miRNA biogenesis. RNA, 2019, 25(1): 1-16.
11.	Zhou J, Yu L, Gao X, et al. Plasma microRNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma. J Clin Oncol, 2011, 29(36): 4781-4788.
12.	Ahmed MY, Salah MM, Kassim SK, et al. Evaluation of the diagnostic and therapeutic roles of non-coding RNA and cell proliferation related gene association in hepatocellular carcinoma. Gene, 2019, 706: 97-105.
13.	Zhang W, Liu K, Liu S, et al. MicroRNA-744 inhibits migration and invasion of hepatocellular carcinoma cells by targeting SOX12. Oncol Rep, 2018, 40(6): 3585-3592.
14.	Bi JG, Zheng JF, Li Q, et al. MicroRNA-181a-5p suppresses cell proliferation by targeting Egr1 and inhibiting Egr1/TGF-β/Smad pathway in hepatocellular carcinoma. Int J Biochem Cell Biol, 2019, 106: 107-116.
15.	Yao X, Zhang H, Liu Y, et al. miR-99b-3p promotes hepatocellular carcinoma metastasis and proliferation by targeting protocadherin 19. Gene, 2019, 698: 141-149.
16.	Wang X, Lu J, Cao J, et al. MicroRNA-18a promotes hepatocellular carcinoma proliferation, migration, and invasion by targeting Bcl2L10. Onco Targets Ther, 2018, 11: 7919-7934.
17.	Tricoli L, Niture S, Chimeh U, et al. Role of microRNAs in the development of hepatocellular carcinoma and drug resistance. Front Biosci (Landmark Ed), 2019, 24: 382-391.
18.	Li Y, Di C, Li W, et al. Oncomirs miRNA-221/222 and tumor suppressors miRNA-199a/195 are crucial miRNAs in liver cancer: a systematic analysis. Dig Dis Sci, 2016, 61(8): 2315-2327.
19.	Xu Y, Huang J, Ma L, et al. MicroRNA-122 confers sorafenib resistance to hepatocellular carcinoma cells by targeting IGF-1R to regulate RAS/RAF/ERK signaling pathways. Cancer Lett, 2016, 371(2): 171-181.
20.	Ohta K, Hoshino H, Wang J, et al. MicroRNA-93 activates c-Met/PI3K/Akt pathway activity in hepatocellular carcinoma by directly inhibiting PTEN and CDKN1A. Oncotarget, 2015, 6(5): 3211-3224.
21.	Martin del Campo SE, Levine KM, Mundy-Bosse BL, et al. The Raf kinase inhibitor sorafenib inhibits JAK-STAT signal transduction in human immune cells. J Immunol, 2015, 195(5): 1995-2005.
22.	Zhang M, Zhang H, Hong H, et al. MiR-374b re-sensitizes hepatocellular carcinoma cells to sorafenib therapy by antagonizing PKM2-mediated glycolysis pathway. Am J Cancer Res, 2019, 9(4): 765-778.
23.	Li W, Qiu Y, Hao J, et al. Dauricine upregulates the chemosensitivity of hepatocellular carcinoma cells: Role of repressing glycolysis via miR-199a: HK2/PKM2 modulation. Food Chem Toxicol, 2018, 121: 156-165.
24.	Shimizu S, Takehara T, Hikita H, et al. The let-7 family of microRNAs inhibits Bcl-xL expression and potentiates sorafenib-induced apoptosis in human hepatocellular carcinoma. J Hepatol, 2010, 52(5): 698-704.
25.	Bonneau E, Neveu B, Kostantin E, et al. How close are miRNAs from clinical practice? A perspective on the diagnostic and therapeutic market. EJIFCC, 2019, 30(2): 114-127.
26.	Zhang J, Li WY, Yang Y, et al. LncRNA XIST facilitates cell growth, migration and invasion via modulating H3 histone methylation of DKK1 in neuroblastoma. Cell Cycle, 2019, 18(16): 1882-1892.
27.	Niederer RO, Hass EP, Zappulla DC. Long noncoding RNAs in the yeast S. cerevisiae. Adv Exp Med Biol, 2017, 1008: 119-132.
28.	Luk AC, Chan WY, Rennert OM, et al. Long noncoding RNAs in spermatogenesis: insights from recent high-throughput transcriptome studies. Reproduction, 2014, 147(5): R131-R141.
29.	Wang S, Jiang J, Zhang C, et al. Serum lincRNA-p21 expression in primary liver diseases and liver metastatic diseases. Pathol Res Pract, 2019, 215(4): 779-783.
30.	Zhang F, Ding L, Cui L, et al. Identification of long non-coding RNA-related and -coexpressed mRNA biomarkers for hepatocellular carcinoma. BMC Med Genomics, 2019, 12(Suppl 1): 25.
31.	Sun J, Guo Y, Bie B, et al. Silencing of long noncoding RNA HOXD-AS1 inhibits proliferation, cell cycle progression, migration and invasion of hepatocellular carcinoma cells through MEK/ERK pathway. J Cell Biochem, 2020, 121(1): 443-457.
32.	Shi Z, Wei D, Wu H, et al. Long non-coding RNA snaR is involved in the metastasis of liver cancer possibly through TGF-β1. Oncol Lett, 2019, 17(6): 5565-5571.
33.	Li J, Zhai DS, Huang Q, et al. LncRNA DCST1-AS1 accelerates the proliferation, metastasis and autophagy of hepatocellular carcinoma cell by AKT/mTOR signaling pathways. Eur Rev Med Pharmacol Sci, 2019, 23(14): 6091-6104.
34.	Zhang J, Li Z, Liu L, et al. Long noncoding RNA TSLNC8 is a tumor suppressor that inactivates the interleukin-6/STAT3 signaling pathway. Hepatology, 2018, 67(1): 171-187.
35.	Zheng Z, Gao Y. Down-regulation of lncRNA snaR is correlated with postoperative distant recurrence of HPV-negative cervical squamous cell carcinoma. Biosci Rep, 2018, 38(6): pii: BSR20181213.
36.	Jin W, Chen L, Cai X, et al. Long non-coding RNA TUC338 is functionally involved in sorafenib-sensitized hepatocarcinoma cells by targeting RASAL1. Oncol Rep, 2017, 37(1): 273-280.
37.	Li W, Dong X, He C, et al. LncRNA SNHG1 contributes to sorafenib resistance by activating the Akt pathway and is positively regulated by miR-21 in hepatocellular carcinoma cells. J Exp Clin Cancer Res, 2019, 38(1): 183.
38.	Zhang PF, Wang F, Wu J, et al. LncRNA SNHG3 induces EMT and sorafenib resistance by modulating the miR-128/CD151 pathway in hepatocellular carcinoma. J Cell Physiol, 2019, 234(3): 2788-2794.
39.	Sui C, Dong Z, Yang C, et al. LncRNA FOXD2-AS1 as a competitive endogenous RNA against miR-150-5p reverses resistance to sorafenib in hepatocellular carcinoma. J Cell Mol Med, 2019, 23(9): 6024-6033.
40.	Tang S, Tan G, Jiang X, et al. An artificial lncRNA targeting multiple miRNAs overcomes sorafenib resistance in hepatocellular carcinoma cells. Oncotarget, 2016, 7(45): 73257-73269.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Wang P, Tan G, Zhu M, et al. Hand-foot skin reaction is a beneficial indicator of sorafenib therapy for patients with hepatocellular carcinoma: a systemic review and meta-analysis. Expert Rev Gastroenterol Hepatol, 2018, 12(1): 1-8.
3. Gezer U, Özgür E, Cetinkaya M, et al. Long non-coding RNAs with low expression levels in cells are enriched in secreted exosomes. Cell Biol Int, 2014, 38(9): 1076-1079.
4. Skuratovskaia D, Vulf M, Komar A, et al. Promising directions in atherosclerosis treatment based on epigenetic regulation using microRNAs and long noncoding RNAs. Biomolecules, 2019, 9(6): pii: E226.
5. Chen W, Liu D, Li QZ, et al. The function of ncRNAs in rheumatic diseases. Epigenomics, 2019, 11(7): 821-833.
6. Wang Y, Chen F, Zhao M, et al. The long noncoding RNA HULC promotes liver cancer by increasing the expression of the HMGA2 oncogene via sequestration of the microRNA-186. J Biol Chem, 2017, 292(37): 15395-15407.
7. Braicu C, Zimta AA, Harangus A, et al. The function of non-coding RNAs in lung cancer tumorigenesis. Cancers (Basel), 2019, 11(5): pii: E605.
8. Huang W, Su G, Huang X, et al. Long noncoding RNA PCAT6 inhibits colon cancer cell apoptosis by regulating anti-apoptotic protein ARC expression via EZH2. Cell Cycle, 2019, 18(1): 69-83.
9. Zhang J, Shi K, Huang W, et al. The DNA methylation profile of non-coding RNAs improves prognosis prediction for pancreatic adenocarcinoma. Cancer Cell Int, 2019, 19: 107.
10. Michlewski G, Cáceres JF. Post-transcriptional control of miRNA biogenesis. RNA, 2019, 25(1): 1-16.
11. Zhou J, Yu L, Gao X, et al. Plasma microRNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma. J Clin Oncol, 2011, 29(36): 4781-4788.
12. Ahmed MY, Salah MM, Kassim SK, et al. Evaluation of the diagnostic and therapeutic roles of non-coding RNA and cell proliferation related gene association in hepatocellular carcinoma. Gene, 2019, 706: 97-105.
13. Zhang W, Liu K, Liu S, et al. MicroRNA-744 inhibits migration and invasion of hepatocellular carcinoma cells by targeting SOX12. Oncol Rep, 2018, 40(6): 3585-3592.
14. Bi JG, Zheng JF, Li Q, et al. MicroRNA-181a-5p suppresses cell proliferation by targeting Egr1 and inhibiting Egr1/TGF-β/Smad pathway in hepatocellular carcinoma. Int J Biochem Cell Biol, 2019, 106: 107-116.
15. Yao X, Zhang H, Liu Y, et al. miR-99b-3p promotes hepatocellular carcinoma metastasis and proliferation by targeting protocadherin 19. Gene, 2019, 698: 141-149.
16. Wang X, Lu J, Cao J, et al. MicroRNA-18a promotes hepatocellular carcinoma proliferation, migration, and invasion by targeting Bcl2L10. Onco Targets Ther, 2018, 11: 7919-7934.
17. Tricoli L, Niture S, Chimeh U, et al. Role of microRNAs in the development of hepatocellular carcinoma and drug resistance. Front Biosci (Landmark Ed), 2019, 24: 382-391.
18. Li Y, Di C, Li W, et al. Oncomirs miRNA-221/222 and tumor suppressors miRNA-199a/195 are crucial miRNAs in liver cancer: a systematic analysis. Dig Dis Sci, 2016, 61(8): 2315-2327.
19. Xu Y, Huang J, Ma L, et al. MicroRNA-122 confers sorafenib resistance to hepatocellular carcinoma cells by targeting IGF-1R to regulate RAS/RAF/ERK signaling pathways. Cancer Lett, 2016, 371(2): 171-181.
20. Ohta K, Hoshino H, Wang J, et al. MicroRNA-93 activates c-Met/PI3K/Akt pathway activity in hepatocellular carcinoma by directly inhibiting PTEN and CDKN1A. Oncotarget, 2015, 6(5): 3211-3224.
21. Martin del Campo SE, Levine KM, Mundy-Bosse BL, et al. The Raf kinase inhibitor sorafenib inhibits JAK-STAT signal transduction in human immune cells. J Immunol, 2015, 195(5): 1995-2005.
22. Zhang M, Zhang H, Hong H, et al. MiR-374b re-sensitizes hepatocellular carcinoma cells to sorafenib therapy by antagonizing PKM2-mediated glycolysis pathway. Am J Cancer Res, 2019, 9(4): 765-778.
23. Li W, Qiu Y, Hao J, et al. Dauricine upregulates the chemosensitivity of hepatocellular carcinoma cells: Role of repressing glycolysis via miR-199a: HK2/PKM2 modulation. Food Chem Toxicol, 2018, 121: 156-165.
24. Shimizu S, Takehara T, Hikita H, et al. The let-7 family of microRNAs inhibits Bcl-xL expression and potentiates sorafenib-induced apoptosis in human hepatocellular carcinoma. J Hepatol, 2010, 52(5): 698-704.
25. Bonneau E, Neveu B, Kostantin E, et al. How close are miRNAs from clinical practice? A perspective on the diagnostic and therapeutic market. EJIFCC, 2019, 30(2): 114-127.
26. Zhang J, Li WY, Yang Y, et al. LncRNA XIST facilitates cell growth, migration and invasion via modulating H3 histone methylation of DKK1 in neuroblastoma. Cell Cycle, 2019, 18(16): 1882-1892.
27. Niederer RO, Hass EP, Zappulla DC. Long noncoding RNAs in the yeast S. cerevisiae. Adv Exp Med Biol, 2017, 1008: 119-132.
28. Luk AC, Chan WY, Rennert OM, et al. Long noncoding RNAs in spermatogenesis: insights from recent high-throughput transcriptome studies. Reproduction, 2014, 147(5): R131-R141.
29. Wang S, Jiang J, Zhang C, et al. Serum lincRNA-p21 expression in primary liver diseases and liver metastatic diseases. Pathol Res Pract, 2019, 215(4): 779-783.
30. Zhang F, Ding L, Cui L, et al. Identification of long non-coding RNA-related and -coexpressed mRNA biomarkers for hepatocellular carcinoma. BMC Med Genomics, 2019, 12(Suppl 1): 25.
31. Sun J, Guo Y, Bie B, et al. Silencing of long noncoding RNA HOXD-AS1 inhibits proliferation, cell cycle progression, migration and invasion of hepatocellular carcinoma cells through MEK/ERK pathway. J Cell Biochem, 2020, 121(1): 443-457.
32. Shi Z, Wei D, Wu H, et al. Long non-coding RNA snaR is involved in the metastasis of liver cancer possibly through TGF-β1. Oncol Lett, 2019, 17(6): 5565-5571.
33. Li J, Zhai DS, Huang Q, et al. LncRNA DCST1-AS1 accelerates the proliferation, metastasis and autophagy of hepatocellular carcinoma cell by AKT/mTOR signaling pathways. Eur Rev Med Pharmacol Sci, 2019, 23(14): 6091-6104.
34. Zhang J, Li Z, Liu L, et al. Long noncoding RNA TSLNC8 is a tumor suppressor that inactivates the interleukin-6/STAT3 signaling pathway. Hepatology, 2018, 67(1): 171-187.
35. Zheng Z, Gao Y. Down-regulation of lncRNA snaR is correlated with postoperative distant recurrence of HPV-negative cervical squamous cell carcinoma. Biosci Rep, 2018, 38(6): pii: BSR20181213.
36. Jin W, Chen L, Cai X, et al. Long non-coding RNA TUC338 is functionally involved in sorafenib-sensitized hepatocarcinoma cells by targeting RASAL1. Oncol Rep, 2017, 37(1): 273-280.
37. Li W, Dong X, He C, et al. LncRNA SNHG1 contributes to sorafenib resistance by activating the Akt pathway and is positively regulated by miR-21 in hepatocellular carcinoma cells. J Exp Clin Cancer Res, 2019, 38(1): 183.
38. Zhang PF, Wang F, Wu J, et al. LncRNA SNHG3 induces EMT and sorafenib resistance by modulating the miR-128/CD151 pathway in hepatocellular carcinoma. J Cell Physiol, 2019, 234(3): 2788-2794.
39. Sui C, Dong Z, Yang C, et al. LncRNA FOXD2-AS1 as a competitive endogenous RNA against miR-150-5p reverses resistance to sorafenib in hepatocellular carcinoma. J Cell Mol Med, 2019, 23(9): 6024-6033.
40. Tang S, Tan G, Jiang X, et al. An artificial lncRNA targeting multiple miRNAs overcomes sorafenib resistance in hepatocellular carcinoma cells. Oncotarget, 2016, 7(45): 73257-73269.

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