LINC00839 promotes malignancy of liver cancer via binding FMNL2 under hypoxia

Abstract

Liver cancer is one of the most common malignant tumors in the world and metastasis is the leading cause of death associated with liver cancer. Hypoxia is a common feature of solid tumors and enhances malignant character of cancer cells. However, the exact mechanisms involved in hypoxia-driven liver cancer progression and metastasis have not been well clarified so far. The aim of this study was to investigate the contribution of long non-coding RNA (lncRNA) in hypoxia promoting liver cancer progression. We screened and revealed LINC00839 as a novel hypoxia-responsive lncRNA in liver cancer. LINC00839 expression was up-regulated in liver cancer tissues and cell lines, and the patients with high LINC00839 expression had shortened overall survival. LINC00839 further overexpressed under hypoxia and promoted liver cancer cell proliferation, migration, and invasion. Mechanistically, LINC00839 bound multiple proteins that were primarily associated with the metabolism and RNA transport, and positively regulated the expression of Formin-like protein 2 (FMNL2). LINC00839 could promote hypoxia-mediated liver cancer progression, suggesting it may be a clinically valuable biomarker and serve as a molecular target for the diagnosis, prognosis, and therapy of liver cancer.

LINC00839 in Human Disorders: Insights into its Regulatory Roles and Clinical Impact, with a Special Focus on Cancer

“…The increased LINC00839 in liver cancer cell lines, combined with its pivotal oncogenic role in driving HCC development, has been well documented in vitro [36,37]. Xie et al [37] unveiled LINC00839 as a novel hypoxia-responsive long non-coding RNA in liver cancer. Under hypoxic conditions, the overexpression of LINC00839 significantly fueled liver cancer cell proliferation, migration, and invasion.…”

“…Similarly, another study conducted by Zhou et al 36 also found that LINC00839 promoted the malignant phenotype of HCC cells. Mechanistically ( Figure 4 ), LINC00839 promotes liver cancer progression by interacting with multiple proteins primarily linked to metabolism and RNA transport, and further upregulates FMNL2 expression under hypoxic conditions 37 . And LINC00839 can also function as a sponge for miR-144-3p, leading to increased WTAP expression levels 36 .…”

“…And LINC00839 can also function as a sponge for miR-144-3p, leading to increased WTAP expression levels 36 . Given its significant roles, LINC00839 emerges as a potential therapeutic target and a valuable biomarker for HCC 36 , 37 . Further in vivo studies are essential for future investigations.…”

“…Among primary liver cancers, hepatocellular carcinoma (HCC) accounts for around 90% of cases [61]. The increased LINC00839 in liver cancer cell lines, combined with its pivotal oncogenic role in driving HCC development, has been well documented in vitro [36,37]. Xie et al [37] unveiled LINC00839 as a novel hypoxia-responsive long non-coding RNA in liver cancer.…”

“…Remarkably, its involvement has garnered growing interest in tumors. LINC00839 exhibits differential expression and may play important roles in a series of human tumors [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47], including nasopharyngeal, breast and lung cancers. High expression levels of LINC00839 in tumor tissues indicated poor clinical outcomes with unfavorable clinicopathological features and prognosis in tumor patients, including lymph node metastasis, clinical stage, and overall and disease-free survival.…”