RNA-binding protein KHSRP promotes tumor growth and metastasis in non-small cell lung cancer

Abstract

BackgroundKH-type splicing regulatory protein (KHSRP) plays an important role in cancer invasion, but the relevant mechanism is not well known. In the present study, we investigated the function and potential molecular mechanism of KHSRP in non-small cell lung cancer (NSCLC) metastasis and elucidated its clinical significance.MethodsIsobaric tags for relative and absolute quantitation and the SWATH™ approach were combined with nanoliquid chromatography-tandem mass spectrometry analysis to identify metastasis-associated nucleoproteins in NSCLC. Real-time PCR and Western blot were used to screen for metastasis-associated candidate molecules. Gene knockdown and overexpression were used to investigate their functions and molecular mechanisms in lung cancer cells. Coimmunoprecipitation (Co-IP) experiments were performed to identify the interactions between candidate molecules and their interacting proteins. Gene expression and its association with multiple clinicopathologic characteristics were analyzed by immunohistochemistry (IHC) and Western blot in human lung cancer specimens.ResultsKHSRP was identified as a metastasis-associated candidate molecule. In NSCLC cell lines, knockdown of KHSRP significantly reduced lung cancer cell proliferation, migration, and invasion in vitro and in vivo, whereas overexpression of KHSRP did the opposite. Mechanistically, the protein heterogeneous nuclear ribonucleoprotein C (C1/C2) (HNRNPC) was identified to interact with KHSRP using Co-IP experiments. In NSCLC cell lines, overexpression of HNRNPC significantly promoted lung cancer cell proliferation, migration, and invasion in vitro and in vivo. KHSRP and HNRNPC may induce human lung cancer cell invasion and metastasis by activating the IFN-α-JAK-STAT1 signaling pathway. Drastically higher expression levels of KHSRP and HNRNPC were observed in lung cancer tissues compared to those in adjacent noncancerous tissues. Increased KHSRP and HNRNPC expression was significantly associated with advanced tumor stages and metastasis (both lymph node and distant). Kaplan-Meier survival analysis showed that patients with high KHSRP and HNRNPC expression levels were predicted to have the shortest survival times and to have a poor prognosis.ConclusionsKHSRP plays an important role in NSCLC metastasis and may serve as a potential prognostic marker and novel therapeutic target for lung cancer metastasis treatment.

Knockdown of LINC00662 represses AK4 and attenuates radioresistance of oral squamous cell carcinoma

“…However, LINC00662 had no regulatory effects on hnRNPC expression. hnRNPC is a survival-related splicing factor in OSCC [18], and served as the tumor facilitator in non-small cell lung cancer [33], ovarian cancer [16]. The hnRNPC protein is one of the Fig.…”

Identification and validation of a novel prognostic index based on m6A RNA methylation regulators in esophageal carcinoma

“…These ndings suggested that ALKBH5-mTOR pathway may be an available therapeutic pathway for cancer treatment. HNRNPC mainly function as an oncogenic role in cancers [38,39]. Previously, studies found that the abnormally expressed HNRNPC was related to the LBX2-AS1 pathway [40] and JAK-STAT1 signaling pathway [39] in several cancers.…”

“…HNRNPC mainly function as an oncogenic role in cancers [38,39]. Previously, studies found that the abnormally expressed HNRNPC was related to the LBX2-AS1 pathway [40] and JAK-STAT1 signaling pathway [39] in several cancers. But the association between the HNRNPC expression and cell cycle related pathway, pentose phosphate pathway, and p53 signaling pathway was rstly reported here, thus the regulatory mechanisms required to be elucidated in future.…”

Construction of a m6A RNA Methylation Regulator-related Signature for Prognosis and Immune Response in Lung Adenocarcinoma

“…Then, the researchers also discovered the overexpression of HNRNPC dramatically accelerated the proliferation, migration, and invasion of lung cancer cells. Moreover, the elevated expression of HNRNPC was signi cantly related to advanced tumor stages, metastasis, and shorter survival time [55]. IGF2BP1, a target of miR-491-5p, was reported to be signi cantly increased in the expression of NSCLC cells, and promoted tumor cell proliferation, migration, and invasion [56].…”