Long Noncoding RNA MIR4435-2HG Promotes Hepatocellular Carcinoma Proliferation and Metastasis Through the MiR-22-3p/YWHAZ Axis

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2020 Nov 16

PMID 33194037

Citations 19

Authors

Xuanlin Shen

Yuting Ding

Feng Lu

Haitao Yuan

Wenkang Luan

Affiliations

Soon will be listed here.

Abstract

Long noncoding RNAs (lncRNAs) play the critical biological role in many malignant tumours. MIR4435-2HG has been proven to be a novel oncogenic lncRNA. However, the exact role and mechanism of MIR4435-2HG in hepatocellular carcinoma (HCC) remain unclear. Here, we found that MIR4435-2HG is overexpressed in HCC tissue compared to normal controls and that high level of MIR4435-2HG indicates a poorer prognosis in HCC patients. MIR4435-2HG enhances the growth and metastasis ability of HCC cells. MIR4435-2HG promotes the expression of YWHAZ by sponging miR-22-3p to liberate YWHAZ mRNA transcripts. MIR4435-2HG facilitates the proliferation and metastasis of HCC by modulating the miR-22-3p/YWHAZ axis. These results demonstrated the role and mechanism of MIR4435-2HG in malignant progression of HCC. MIR4435-2HG may be used as the prognostic marker and treatment target for the patient with HCC.

Citing Articles

Long non-coding RNA MIR4435-2HG modulates pancreatic cancer stem cells and chemosensitivity to gemcitabine by targeting the miR-1252-5p/STAT1.

Xie B, Wu P, Liu H, Yang X, Huang L J Transl Med. 2025; 23(1):165.

PMID: 39920781 PMC: 11806857. DOI: 10.1186/s12967-025-06128-8.

Inferring single-cell and spatial microRNA activity from transcriptomics data.

Herbst E, Mandel-Gutfreund Y, Yakhini Z, Biran H Commun Biol. 2025; 8(1):87.

PMID: 39827321 PMC: 11743151. DOI: 10.1038/s42003-025-07454-9.

Long non-coding RNA MIR4435-2HG promotes pancreatic cancer progression by regulating ABHD17C through sponging miR-128-3p.

Chen Z, Du Y, Shi H, Dong S, He R, Zhou W Transl Cancer Res. 2024; 13(8):4113-4130.

PMID: 39262472 PMC: 11385540. DOI: 10.21037/tcr-24-51.

Biological Roles and Pathogenic Mechanisms of LncRNA MIR4435-2HG in Cancer: A Comprehensive Review.

Chen Z, Guan D, Zhu Q, Wang Z, Han F, Zhou W Curr Issues Mol Biol. 2023; 45(11):8864-8881.

PMID: 37998733 PMC: 10670187. DOI: 10.3390/cimb45110556.

LncRNA MIR4435-2HG drives cancer progression by modulating cell cycle regulators and mTOR signaling in stroma-enriched subtypes of urothelial carcinoma of the bladder.

Pei L, Yan D, He Q, Kong J, Yang M, Ruan H Cell Oncol (Dordr). 2023; 46(5):1509-1527.

PMID: 37355516 PMC: 10618329. DOI: 10.1007/s13402-023-00826-5.

References

Wallace M, Preen D, Jeffrey G, Adams L . The evolving epidemiology of hepatocellular carcinoma: a global perspective. Expert Rev Gastroenterol Hepatol. 2015; 9(6):765-79. DOI: 10.1586/17474124.2015.1028363. View

Luan W, Ding Y, Ma S, Ruan H, Wang J, Lu F . Long noncoding RNA LINC00518 acts as a competing endogenous RNA to promote the metastasis of malignant melanoma via miR-204-5p/AP1S2 axis. Cell Death Dis. 2019; 10(11):855. PMC: 6848151. DOI: 10.1038/s41419-019-2090-3. View

Zhao L, Hu K, Cao J, Wang P, Li J, Zeng K . lncRNA functions as a ceRNA to upregulate by sponging in HCC cellular senescence. Aging (Albany NY). 2019; 11(17):7098-7122. PMC: 6756895. DOI: 10.18632/aging.102240. View

Luan W, Wang Y, Chen X, Shi Y, Wang J, Zhang J . PKM2 promotes glucose metabolism and cell growth in gliomas through a mechanism involving a let-7a/c-Myc/hnRNPA1 feedback loop. Oncotarget. 2015; 6(15):13006-18. PMC: 4536995. DOI: 10.18632/oncotarget.3514. View

Zhang H, Chen Z, Wang X, Huang Z, He Z, Chen Y . Long non-coding RNA: a new player in cancer. J Hematol Oncol. 2013; 6:37. PMC: 3693878. DOI: 10.1186/1756-8722-6-37. View

Wei G, Hu M, Zhao L, Guo W . MiR-451a suppresses cell proliferation, metastasis and EMT via targeting YWHAZ in hepatocellular carcinoma. Eur Rev Med Pharmacol Sci. 2019; 23(12):5158-5167. DOI: 10.26355/eurrev_201906_18180. View

Zhao J, Zhao Q, Hu H, Liao J, Lin J, Xia C . The ASH1-miR-375-YWHAZ Signaling Axis Regulates Tumor Properties in Hepatocellular Carcinoma. Mol Ther Nucleic Acids. 2018; 11:538-553. PMC: 5944419. DOI: 10.1016/j.omtn.2018.04.007. View

Ni X, Ding Y, Yuan H, Shao J, Yan Y, Guo R . Long non-coding RNA ZEB1-AS1 promotes colon adenocarcinoma malignant progression via miR-455-3p/PAK2 axis. Cell Prolif. 2019; 53(1):e12723. PMC: 6985675. DOI: 10.1111/cpr.12723. View

Zong W, Feng W, Jiang Y, Cao Y, Ke Y, Shi X . LncRNA CTC-497E21.4 promotes the progression of gastric cancer via modulating miR-22/NET1 axis through RhoA signaling pathway. Gastric Cancer. 2019; 23(2):228-240. DOI: 10.1007/s10120-019-00998-w. View

10.

Zhang H, Meng H, Huang X, Tong W, Liang X, Li J . lncRNA MIR4435-2HG promotes cancer cell migration and invasion in prostate carcinoma by upregulating TGF-β1. Oncol Lett. 2019; 18(4):4016-4021. PMC: 6732992. DOI: 10.3892/ol.2019.10757. View

11.

Qian H, Chen L, Huang J, Wang X, Ma S, Cui F . The lncRNA MIR4435-2HG promotes lung cancer progression by activating β-catenin signalling. J Mol Med (Berl). 2018; 96(8):753-764. DOI: 10.1007/s00109-018-1654-5. View

12.

Shen H, Sun B, Yang Y, Cai X, Bi L, Deng L . MIR4435-2HG regulates cancer cell behaviors in oral squamous cell carcinoma cell growth by upregulating TGF-β1. Odontology. 2020; 108(4):553-559. DOI: 10.1007/s10266-020-00488-x. View

13.

Dufour J, Johnson P . Liver cancer: from molecular pathogenesis to new therapies: summary of the EASL single topic conference. J Hepatol. 2009; 52(2):296-304. DOI: 10.1016/j.jhep.2009.11.010. View

14.

Zheng Y, Li L, Jia Y, Zhang B, Li J, Zhu Y . LINC01554-Mediated Glucose Metabolism Reprogramming Suppresses Tumorigenicity in Hepatocellular Carcinoma via Downregulating PKM2 Expression and Inhibiting Akt/mTOR Signaling Pathway. Theranostics. 2019; 9(3):796-810. PMC: 6376468. DOI: 10.7150/thno.28992. View

15.

Tay Y, Rinn J, Pandolfi P . The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014; 505(7483):344-52. PMC: 4113481. DOI: 10.1038/nature12986. View

16.

Ma D, Sun D, Wang J, Jin D, Li Y, Han Y . Long non-coding RNA MIR4435-2HG recruits miR-802 from FLOT2 to promote melanoma progression. Eur Rev Med Pharmacol Sci. 2020; 24(5):2616-2624. DOI: 10.26355/eurrev_202003_20530. View

17.

Chen C, Chuang S, Yang M, Liao J, Yu S, Chen J . A novel function of YWHAZ/β-catenin axis in promoting epithelial-mesenchymal transition and lung cancer metastasis. Mol Cancer Res. 2012; 10(10):1319-31. DOI: 10.1158/1541-7786.MCR-12-0189. View

18.

Ouyang W, Ren L, Liu G, Chi X, Wei H . LncRNA MIR4435-2HG predicts poor prognosis in patients with colorectal cancer. PeerJ. 2019; 7:e6683. PMC: 6450379. DOI: 10.7717/peerj.6683. View

19.

Gutschner T, Diederichs S . The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol. 2012; 9(6):703-19. PMC: 3495743. DOI: 10.4161/rna.20481. View

20.

Altekruse S, Henley S, Cucinelli J, McGlynn K . Changing hepatocellular carcinoma incidence and liver cancer mortality rates in the United States. Am J Gastroenterol. 2014; 109(4):542-53. PMC: 4148914. DOI: 10.1038/ajg.2014.11. View