LINCRNA00273 promotes cancer metastasis and its G-Quadruplex promoter can serve as a novel target to inhibit cancer invasiveness

Abstract

Discovery of anti-metastatic drugs is of immense clinical significance as metastasis is responsible for 90% of all cancer deaths. Here we report the inhibitory effect of a bis schiff base (M2) on cancer cell migration and invasion in vitro and in vivo. M2 has shown good solubility and permeability across the intestinal cell wall and hence can be classified as BCS (Biopharmaceutical classification system) class I. Microarray studies identified a long non coding intergenic RNA, LINC00273 as a novel molecular target of M2. We report that LINC00273 harbors a unique (4n-1) parallel G-Quadruplex structure in its promoter as validated by DMS footprint. M2 is proposed to stabilize this G-quadruplex structure resulting in the down-regulation of LINC00273 expression. Dual Luciferase reporter assay also suggests inhibition of LINC00273 promoter activity by M2. Involvement of this linc in metastasis is proven by siRNA and shRNA mediated knock down of LINC00273 in vitro and in vivo in nude mice which significantly decelerates cancer cell migration and invasion and also makes the cells unresponsive to TGF-β's pro-metastatic effects. Furthermore, the real time expression of LINC00273 in thirty seven human clinical samples is found to be positively correlated with the histopathological staging of metastasis.

Functional Specialization of Human Salivary Glands and Origins of Proteins Intrinsic to Human Saliva

“…Besides genes encoding proteins abundantly found in saliva (e.g., HTN, MUC7, PRB, and AMY1), most of these salivary-gland-specific genes are long non-coding RNAs (108 genes) that to our knowledge have not been identified in the salivary gland context. They include LINC00273, a possible regulator of lung cancer metastasis ( Jana et al, 2017 ), and AC092159.2, which has been suggested to play a role in metabolic processes ( Hu et al, 2019 ). Given the multiple suggested roles of long non-coding RNAs in other organ systems, these transcripts may play a role in controlling nuclear architecture and transcription in the nucleus, as well as in modulating mRNA stability, translation, and posttranslational modifications in the cytoplasm of salivary gland cells.…”

The inhibition of hypoxia‐induced angiogenesis and metastasis by cinnamaldehyde is mediated by decreasing HIF‐1α protein synthesis via PI3K/Akt pathway

“…Migration of B16F10 to secondary organs can be easily detected following histological examination of black clusters of colonized melanoma cells. Scoring of number of colony formation per field examined gives an estimation of the extent of migration . The inhibitory percentage of melanoma cell migration was 35.3 ± 10% and 32.9 ± 7.2% in lung and liver, respectively, following CA treatment (Fig.…”

Tumor‐derived exosomal miR‐19b‐3p facilitates M2 macrophage polarization and exosomal LINC00273 secretion to promote lung adenocarcinoma metastasis via Hippo pathway

“…LINC00273 is recently found to serve oncogenic roles in LC, gastric cancer, and melanoma by promoting metastasis in cancer cells. 28 , 29 However, whether LINC00273 participates in the communication between LUAD cells and M2 macrophages is unknown yet. MiR‐19b‐3p is reported as an oncogenic miRNA in several cancers such as cholangiocarcinoma and pancreatic cancer.…”