LINC00323 knockdown suppresses the proliferation, migration, and vascular mimicry of non-small cell lung cancer cells by promoting ubiquitinated degradation of AKAP1.

Abstract

Background: LINC00323, a new long noncoding RNA, is aberrantly expressed in several cancers. However, the expression, function, and mechanism of LINC00323 in non-small cell lung cancer (NSCLC) are unclear.

Methods: In the present study, LINC00323, VEGFA, microvessel density (MVD), and AKAP1 levels were confirmed in NSCLC tissues. Cell proliferation, migration, and vascular mimicry (VM) were examined to assess the effects of LINC00323 and AKAP1 on NSCLC cells. In addition, the interaction between LINC00323 and AKAP1 was verified by RNA pull-down, LC-MS/MS and RNA immunoprecipitation. The ubiquitination level of AKAP1 was also confirmed through coimmunoprecipitation, cycloheximide (CHX) chase, and ubiquitination assays in vitro.

Results: Our results revealed that LINC00323 was upregulated in NSCLC tissues and was positively correlated with metastasis, poor prognosis, VEGFA expression, elevated MVD, and AKAP1 expression. Functionally, LINC00323 or AKAP1 knockdown suppressed the proliferation, migration, and VM of NSCLC cells. Mechanistically, LINC00323 could target AKAP1, and LINC00323 knockdown accelerated ubiquitination-mediated AKAP1 protein degradation. Moreover, LINC00323 silencing suppressed NSCLC cell progression by downregulating AKAP1.

Conclusions: LINC00323 knockdown prevents NSCLC cell proliferation, migration, and VM formation by targeting AKAP1, indicating that LINC00323 and AKAP1 might be biological targets for NSCLC treatment.