LINC01106 post-transcriptionally regulates ELK3 and HOXD8 to promote bladder cancer progression

Abstract

Bladder cancer (BCa) is a kind of common urogenital malignancy worldwide. Emerging evidence indicated that long noncoding RNAs (lncRNAs) play critical roles in the progression of BCa. In this study, we discovered a novel lncRNA LINC01116 whose expression increased with stages in BCa patients and closely related to the survival rate of BCa patients. However, the molecular mechanism dictating the role of LINC01116 in BCa has not been well elucidated so far. In our study, we detected that the expression of LINC01116 was boosted in BCa cells. Moreover, the results of a series of functional assays showed that LINC01116 knockdown suppressed the proliferation, migration, and invasion of BCa cells. Thereafter, GEPIA indicated the closest correlation of LINC01116 with two protein-coding genes, ELK3 and HOXD8. Interestingly, LINC01116 was mainly a cytoplasmic lncRNA in BCa cells, and it could modulate ELK3 and HOXD8 at post-transcriptional level. Mechanically, LINC01116 increased the expression of ELK3 by adsorbing miR-3612, and also stabilized HOXD8 mRNA by binding with DKC1. Rescue experiments further demonstrated that the restraining influence of LINC01116 knockdown on the progression of BCa, was partly rescued by ELK3 promotion, but absolutely reversed by the co-enhancement of ELK3 and HOXD8. More intriguingly, HOXD8 acted as a transcription factor to activate LINC01116 in BCa. In conclusion, HOXD8-enhanced LINC01116 contributes to the progression of BCa via targeting ELK3 and HOXD8, which might provide new targets for treating patients with BCa.

Identification of the Prognostic Significance of Somatic Mutation-Derived LncRNA Signatures of Genomic Instability in Lung Adenocarcinoma

“…Among the seven GInlncRNAs, LINC01133, LINC01671, LINC01116, FAM83A-AS1, and PLAC4 were risk factors for survival, whereas MIR223HG and AL590226.1 were protective factors for patient prognosis. Of note, LINC01133 ( Zhang et al, 2015 ; Zhai et al, 2020 ; Li et al, 2020 ; Liu and Xi, 2020 ; Yang W. et al, 2020 ), LINC01116 ( Cui et al, 2020 ; Meng et al, 2020 ), and FAM83A-AS1 ( He and Yu, 2019 ; Shi et al, 2019 ; Huang et al, 2020 ) have already been identified to be involved in tumorigenesis and malignant progression in lung cancer or other tumors. For example, Zang et al (2016) reported that the upregulated expression of LINC01133 in NSCLC was associated with poor patient survival.…”

Homeobox Genes in Cancers: From Carcinogenesis to Recent Therapeutic Intervention

“…HOX proteins encoded by HOX genes are key components of substantial metabolic processes such as lipidic metabolism, and their [brain cancer mainly includes the glioma and neuroblastoma (4)(5)(6)(7)(8)(9)(10)(11), lung cancer (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), hepatocellular carcinoma (25)(26)(27)(28)(29)(30)(31), bladder cancer (32,33), cholangiocarcinoma (34), head and neck squamous cell carcinoma (35,36), breast cancer (21)(22)(23)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)…”

“…Regulation of HOX factors in various tumor types described in this figure legend. [brain cancer mainly includes the glioma and neuroblastoma (4-11), lung cancer(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24), hepatocellular carcinoma(25)(26)(27)(28)(29)(30)(31), bladder cancer(32,33), cholangiocarcinoma(34), head and neck squamous cell carcinoma(35,36), breast cancer(21-23, 37- 54), gastric carcinoma and esophagus cancer(55)(56)(57)(58)(59)(60)(61)(62)(63)(64), prostate cancer and renal carcinoma(43,(65)(66)(67)(68)(69)(70)(71)(72), ovarian cancer (73-79), endometrial cancer and cervical cancer(80)(81)(82)(83)(84), leukemia<...>…”

Biological functions and clinical significance of long noncoding RNAs in bladder cancer

“…LINC01116 increases the expression of ELK3 by adsorbing miR-3612 and stabilizes HOXD8 mRNA by binding with DKC1. With the combination of ELK3 and HOXD8, LINC01116 promotes cell proliferation, metastasis, and the EMT process [ 147 ].…”